Binding proteins recognizing HA-2 antigen and uses thereof

Abstract

Abstract Binding proteins comprising T cell receptors (TCRs) that recognize an HA-2 antigen and uses thereof.

Description

Cross-Reference to Related Applications This application claims the benefit of U.S. Provisional Application No. 63 / 174,818, filed on 14 April 2021, U.S. Provisional Application No. 63 / 215,760, filed on 28 June 2021, U.S. Provisional Application No. 63 / 288,078, filed on 10 December 2021, and U.S. Provisional Application No. 63 / 329,560, filed on 11 April 2022; the entire contents of each of said applications are incorporated herein in their entirety by this reference. Background of the Invention Approximately 50% of AML patients relapse following allogeneic hematopoietic stem cell transplant therapy, leaving them with very few treatment options (Rautenberg et al. (2019) Int. J. Mol. Sci. 20:228). Rare patients who naturally develop a minor antigenspecific graft-versus-leukemia T cell response show substantially lower relapse rates (Marijt (2003) Proc. Natl. Acad. Sci. U.S.A. 100:2742-2747; Spierings et al. (2013) Biol. Blood Marrow Transplant. 19:1244-1253). HA-2 (YIGEVLVSV, genotype RS 61739531 C / C or T / C) is an HLA-A*02:01- and hematopoietically-restricted minor histocompatibility antigen (derived from the class I myosin protein, MY01G; Pierce et al. (2001) J. Immunol. 167:3223-3230), making it an ideal candidate for TCR immunotherapy of liquid tumors. Patients receiving donor lymphocyte infusion from HA-2 mismatched donors who develop HA-2-specific T cells show a graft vs leukemia response and experience long-term remission (Marijt et al. (2003) Proc. Natl. Acad. Sci. U.S.A. 100:2742-2747). There is a need for developing HA-2-specific TCR immunotherapy, such as to treat disorders characterized by expression of an HA-2 antigen. Summary of the Invention The present invention is based, at least in part, on the discovery of binding proteins, including T cell receptors (TCRs), that recognize an HA-2 antigen (e.g., YIGEVLVSV and / or YIGEVLVSM). In one aspect, a binding protein comprising: a) a T cell receptor (TCR) alpha chain CDR sequence with at least about 80% identity to a TCR alpha chain CDR sequence selected from the group consisting of TCR alpha chain CDR sequences listed in Table 1; and / or b) a TCR beta chain CDR sequence with at least about 80% identity to a TCR beta chain CDR sequence selected from the group consisting of TCR beta chain CDR sequences 2023204645   13 Jul 2023 listed in Table 1, wherein the binding protein is capable of binding to an HA-2 immunogenic peptide-MHC (pMHC) complex, optionally wherein the binding affinity has a Ka less than or equal to about 5xl0-4 M, is provided. In another aspect, a binding protein comprising: a) a TCR alpha chain variable (Va) 5 domain sequence with at least about 80% identity to a TCR Va domain sequence selected from the group consisting of TCR Va domain sequences listed in Table 1; and / or b) a TCR beta chain variable (Vp) domain sequence with at least about 80% identity to a TCR Vp domain sequence selected from the group consisting of TCR Vp domain sequences listed in Table 1, wherein the binding protein is capable of binding to an HA-2 immunogenic 10 peptide-MHC (pMHC) complex, optionally wherein the binding affinity has a Kd less than or equal to about 5x10’4 M, is provided. In still another aspect, a binding protein comprising: a) a TCR alpha chain sequence with at least about 80% identity to a TCR alpha chain sequence selected from the group consisting of TCR alpha chain sequences listed in Table 1; and / or b) a TCR beta chain 15 sequence with at least about 80% identity to a TCR beta chain sequence selected from the group consisting of TCR beta chain sequences listed in Table 1, wherein the binding protein is capable of binding to an HA-2 immunogenic peptide-MHC (pMHC) complex, optionally wherein the binding affinity has a Kd less than or equal to about 5xl0-4 M, is provided. In yet another aspect, a binding protein comprising: a) a TCR alpha chain CDR 20 sequence selected from the group consisting of TCR alpha chain CDR sequences listed in Table 1; and / or b) a TCR beta chain CDR sequence selected from the group consisting of TCR beta chain CDR sequences listed in Table 1, wherein the binding protein is capable of binding to an HA-2 immunogenic peptide-MHC (pMHC) complex, optionally wherein the binding affinity has a Kd less than or equal to about 5xl0-4 M, is provided. 25          In another aspect, a binding protein comprising: a) a TCR alpha chain variable (Va) domain sequence selected from the group consisting of TCR Va domain sequences listed in Table 1; and / or b) a TCR beta chain variable (Vp) domain sequence selected from the group consisting of TCR Vp domain sequences listed in Table 1, wherein the binding protein is capable of binding to an HA-2 immunogenic peptide-MHC (pMHC) complex, optionally 30 wherein the binding affinity has a Kd less than or equal to about 5xl0-4 M, is provided. In still another aspect, a binding protein comprising: a) a TCR alpha chain sequence selected from the group consisting of TCR alpha chain sequences listed in Table 1; and / or b) a TCR beta chain sequence selected from the group consisting of TCR beta chain 2023204645   13 Jul 2023 sequences listed in Table 1, wherein the binding protein is capable of binding to an HA-2 immunogenic peptide-MHC (pMHC) complex, optionally wherein the binding affinity has a Ka less than or equal to about 5xl0-4 M, is provided. Numerous embodiments are further provided that may be applied to any aspect encompassed by the present invention and / or combined with any other embodiment described herein. For example, in one embodiment, 1) a TCR alpha chain CDR, TCR Va domain, and / or TCR alpha chain is encoded by a TRAV, TRAJ, and / or TRAC gene or fragment thereof selected from the group of TRAV, TRAJ, and TRAC genes listed in Table 1, and / or 2) a TCR beta chain CDR, TCR Vp domain, and / or TCR beta chain is encoded by a TRBV, TRBJ, and / or TRBC gene or fragment thereof selected from the group of TRBV, TRBJ, and TRBC genes listed in Table 1, and / or 3) each CDR of the binding protein has up to five amino acid substitutions, insertions, deletions, or a combination thereof as compared to the cognate reference CDR sequence listed in Table 1, is provided. In another embodiment, an HA-2 immunogenic peptide comprises the amino acid sequence YIGEVLVSV or YIGEVLVSM. In still another embodiment, a binding protein is chimeric, humanized, or human. In yet another embodiment, a binding protein is a TCR, an antigen-binding fragment of a TCR, a single chain TCR (scTCR), a chimeric antigen receptor (CAR), or a fusion protein comprising a TCR and an effector domain, optionally wherein the binding domain comprises a transmembrane domain and an effector domain that is intracellular. In yet another embodiment, a TCR alpha chain and a TCR beta chain are covalently linked, optionally wherein the TCR alpha chain and the TCR beta chain are covalently linked through a linker peptide. In another embodiment, a TCR alpha chain and / or a TCR beta chain are covalently linked to a moiety, optionally wherein the covalently linked moiety comprises an affinity tag or a label. In still another embodiment, an affinity tag is selected from the group consisting of CD34 enrichment tag, Glutathione-S-Transferase (GST), calmodulin binding protein (CBP), protein C tag, Myc tag, HaloTag, HA tag, Flag tag, His tag, biotin tag, and V5 tag, and / or wherein the label is a fluorescent protein. In yet another embodiment, a covalently linked moiety is selected from the group consisting of an inflammatory agent, cytokine, toxin, cytotoxic molecule, radioactive isotope, or antibody or antigen-binding fragment thereof. In another embodiment, a binding protein binds to a pMHC complex on a cell surface. In still another embodiment, an MHC is a MHC multimer, optionally wherein the MHC multimer is a tetramer. In yet another embodiment, an MHC is a MHC class I molecule. In another embodiment, an 2023204645   13 Jul 2023 MHC comprises an MHC alpha chain that is an HLA serotype HLA-A*02. In still another embodiment, an HLA allele is selected from the group consisting of HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0205, HLA-A*0206, and HLA-A*0207 allele. In yet another embodiment, binding of a binding protein described herein to an HA-2 peptide - 5 MHC (pMHC) complex elicits an immune response, optionally wherein the immune response is a T cell response. In another embodiment, a T cell response is selected from the group consisting of T cell expansion, cytokine release, and / or cytotoxic killing. In still another embodiment, a binding protein is capable of specifically binding to the HA-2 immunogenic peptide-MHC (pMHC) complex with a Kdless than or equal to about IxlO-4 10 M, less than or equal to about 5xl0-5 M, less than or equal to about IxlO-5 M, less than or equal to about 5x1 O’6 M, less than or equal to about IxlO-6 M, less than or equal to about 5xl0-7 M, less than or equal to about IxlO-7 M, less than or equal to about 5xl0-8 M, less than or equal to about IxlO-8 M, less than or equal to about 5xl0-9 M, less than or equal to about IxlO-9 M, less than or equal to about 5xlO-10 M, less than or equal to about IxlO-10 15 M, less than or equal to about 5xl0-11 M, less than or equal to about IxlO-11 M, less than or equal to about 5xl0-12 M, or less than or equal to about IxlO-12 M. In yet another embodiment, a binding protein has a higher binding affinity to the peptide-MHC (pMHC) than does a known T-cell receptor. In another embodiment, a binding protein has at least 1.05-fold higher binding affinity to the peptide-MHC (pMHC) than does a known T-cell 20 receptor. In still another embodiment, a binding protein induces higher T cell expansion, cytokine release, and / or cytotoxic killing than does a known T-cell receptor when contacted with target cells with a heterozygous expression of HA-2. In yet another embodiment, a binding protein induces at least 1.05-fold increase in T cell expansion, cytokine release, and / or cytotoxic killing than does a known T-cell receptor when contacted with target cells 25 with a heterozygous expression of HA-2. As used herein, references to fold changes, in some embodiments, may be in comparison to any reference modality of interest, such as comparison to a different binding protein; comparison tothe same bindng protein under different context like expression of the same binding protein in a different immune cell, at a different level, in combination with other agents described herein; and the like. In another 30 embodiment, a target cell is a DEL, THP-1, or TF-1 cell line. In still another embodiment, a target cell is a cancer cell. In yet another embodiment, a cancer is a hematological malignancy. In another embodiment, a hematological malignancy is a leukemia, a lymphoma, a myelodysplastic disorder, a myeloproliferative neoplasm, or a myeloma. 2023204645   13 Jul 2023 In yet another aspect, a TCR alpha chain and / or beta chain selected from the group consisting of TCR alpha chain and beta chain sequences listed in Table 1, is provided. In another aspect, an isolated nucleic acid molecule that hybridizes, under stringent conditions, with the complement of a nucleic acid encoding a polypeptide selected from the group consisting of polypeptide sequences listed in Table 1, or a sequence with at least about 80% homology to a nucleic acid encoding a polypeptide selected from the group consisting of the polypeptide sequences listed in Table 1, optionally wherein the isolated nucleic acid molecule comprises 1) a TRAV, TRAJ, and / or TRAC gene or fragment thereof selected from the group of TRAV, TRAJ, and TRAC genes listed in Table 1 and / or 2) a TRBV, TRBJ, and / or TRBC gene or fragment thereof selected from the group of TRBV, TRBJ, and TRBC genes listed in Table 1, is provided. Numerous embodiments are further provided that may be applied to any aspect encompassed by the present invention and / or combined with any other embodiment described herein. For example, in one embodiment, a nucleic acid is codon optimized for expression in a host cell. In still another aspect, a vector comprising an isolated nucleic acid described herein, is provided. Numerous embodiments are further provided that may be applied to any aspect encompassed by the present invention and / or combined with any other embodiment described herein. For example, in one embodiment, a vector is a cloning vector, expression vector, or viral vector. In another embodiment, a vector further comprises nucleic acid sequence encoding CD8a and / or CD8p. In still another embodiment, a nucleic acid sequence encoding CD8a or CD8P is operably linked to a nucleic acid encoding a tag. In yet another embodiment, a nucleic acid encoding a tag is at the 5’ upstream of the nucleic acid sequence encoding CD8a or CD8P such that the tag is fused to the N-terminus of CD8a or CD8p. In another embodiment, a tag is a CD34 enrichment tag. In still another embodiment, an isolated nucleic acid described herein, and the nucleic acid sequence encoding CD8a and / or CD8P are interconnected with an internal ribosome entry site or a nucleic acid sequence encoding a self-cleaving peptide. In yet another embodiment, a selfcleaving peptide is P2A, E2A, F2A or T2A. In yet another aspect, a host cell which comprises an isolated nucleic acid described herein, comprises a vector described herein, and / or expresses a binding protein described herein, optionally wherein the cell is genetically engineered, is provided. 2023204645   13 Jul 2023 Numerous embodiments are further provided that may be applied to any aspect encompassed by the present invention and / or combined with any other embodiment described herein. For example, in one embodiment, a host cell comprises a chromosomal gene knockout of a TCR gene, an HLA gene, or both. In still another embodiment, a host 5 cell comprises a knockout of an HLA gene selected from an al macroglobulin gene, a2 macroglobulin gene, a3 macroglobulin gene, 01 microglobulin gene, 02 microglobulin gene, and combinations thereof. In yet another embodiment, a host cell comprises a knockout of a TCR gene selected from a TCR a variable region gene, TCR 0 variable region gene, TCR constant region gene, and combinations thereof. In another embodiment, 10 a host cell expresses CD8a and / or CD80. In still another embodiment, a CD8a and / or CD80 is fused to a CD34 enrichment tag. In yet another embodiment, host cells are enriched using a CD34 enrichment tag. In another embodiment, a host cell is a hematopoietic progenitor cell, peripheral blood mononuclear cell (PBMC), cord blood cell, or immune cell. In another embodiment, an immune cell is a cytotoxic lymphocyte, 15 cytotoxic lymphocyte precursor cell, cytotoxic lymphocyte progenitor cell, cytotoxic lymphocyte stem cell, CD4+ T cell, CD8+ T cell, CD4 / CD8 double negative T cell, gamma delta (y8) T cell, natural killer (NK) cell, NK-T cell, dendritic cell, or combination thereof. In still another embodiment, a T cell is a naive T cell, central memory T cell, effector memory T cell, or a combination thereof. In yet another embodiment, a T cell is a primary 20 T cell or a cell of a T cell line. In another embodiment, a T cell does not express or has a lower surface expression of an endogenous TCR. In still another embodiment, a host cell is capable of producing a cytokine or a cytotoxic molecule when contacted with a target cell that comprises a peptide-MHC (pMHC) complex comprising the HA-2 peptide epitope in the context of an MHC molecule. In yet another embodiment, a host cell is contacted with 25 the target cell in vitro, ex vivo, or in vivo. In another embodiment, a cytokine is TNF-a, IL-2, and / or IFN-y. In still another embodiment, a cytotoxic molecule is perforins and / or granzymes, optionally wherein the cytotoxic molecule is granzyme B. In yet another embodiment, a host cell is capable of producing a higher level of cytokine or a cytotoxic molecule when contacted with a target cell with a heterozygous expression of HA-2. In 30 another embodiment, a host cell is capable of producing an at least 1.05-fold higher level of cytokine or a cytotoxic molecule. In still another embodiment, a host cell is capable of killing a target cell that comprises a peptide-MHC (pMHC) complex comprising the HA-2 peptide epitope in the context of an MHC molecule. In yet another embodiment, killing is 2023204645   13 Jul 2023 determined by a killing assay. In another embodiment, a ratio of a host cell and a target cell in a killing assay is from 20:1 to 0.625:1. In still another embodiment, a target cell is a T2 cell pulsed with 1 pg / mL to 50 pg / mL of HA-2 peptide. In yet another embodiment, a host cell is capable of killing a higher number of target cells when contacted with target cells with a heterozygous expression of HA-2. In another embodiment, a host cell is capable of killing an at least 1.05-fold higher number of target cells. In still another embodiment, a target cell is a DEL, THP-1, or TF-1 cell line. In yet another embodiment, an HA-2 immunogenic peptide comprises the amino acid sequence YIGEVLVSV or YIGEVLVSM. In another embodiment, an MHC molecule is a MHC class I molecule. In still another embodiment, an MHC molecule comprises an MHC alpha chain that is an HLA serotype HLA-A* 02. In yet another embodiment, an HLA allele is selected from the group consisting of HLA-A*02:01, HLA-A*0202, HLA-A*0203, HLA-A*0205, HLA-A*0206, and HLA-A*0207 allele. In another embodiment, a target cell is a cell line selected from the group consisting of Del, THP-1, and TF-1 cell lines, is a hematopoietic cancer cell expressing HA-2, or is not NB4. In still another embodiment, a cancer cell is of a hematological malignancy selected from the group consisting of a leukemia, a lymphoma, a myelodysplastic disorder, a myeloproliferative neoplasm, or myeloma. In yet another embodiment, a host cell does not express HA-2 antigen, is not recognized by a binding protein described herein, is not of serotype HLA-A*02, and / or does not express an HLA-A*02 allele. In another aspect, a population of host cells described herein, is provided. In still another aspect, a composition comprising: a) a binding protein described herein, b) an isolated nucleic acid described herein, c) a vector described herein, d) a host cell described herein, and / or e) a population of host cells described herein, and a carrier, is provided. In yet another aspect, a device or kit comprising: a) a binding protein described herein, b) an isolated nucleic acid described herein, c) a vector described herein, d) a host cell described herein, and / or e) a population of host cells described herein, said device or kit optionally comprising a reagent to detect binding of a), d) and / or e) to a pMHC complex, is provided. In another aspect, a method of producing a binding protein described herein, wherein the method comprises the steps of: (i) culturing a transformed host cell which has been transformed by a nucleic acid comprising a sequence encoding a binding protein 2023204645   13 Jul 2023 described herein under conditions suitable to allow expression of said binding protein; and (ii) recovering the expressed binding protein, is provided. In still another aspect, a method of producing a host cell expressing a binding protein described herein, wherein the method comprises the steps of: (i) introducing a 5 nucleic acid comprising a sequence encoding a binding protein described herein into the host cell; (ii) culturing the transformed host cell under conditions suitable to allow expression of said binding protein, is provided. In yet another aspect, a method of detecting the presence or absence of an HA-2 antigen and / or a cell expressing HA-2, optionally wherein the cell is a hyperproliferative 10 cell, comprising detecting the presence or absence of said HA-2 antigen in a sample by use of at least one binding protein described herein, or at least one host cell described herein, wherein detection of the HA-2 antigen is indicative of the presence of an HA-2 antigen and / or cell expressing HA-2, is provided. Numerous embodiments are further provided that may be applied to any aspect 15 encompassed by the present invention and / or combined with any other embodiment described herein. For example, in one embodiment, at least one binding protein described herein, or at least one host cell described herein, forms a complex with an HA-2 peptide in the context of an MHC molecule, and the complex is detected in the form of fluorescence activated cell sorting (FACS), enzyme linked immunosorbent assay (ELISA), radioimmune 20 assay (RIA), immunochemically, Western blot, or intracellular flow assay. In another embodiment, a method further comprises obtaining a sample from a subject. In still another embodiment, a method further comprises confirming cells expressing HA-2 by bone marrow biopsy. In another aspect, a method of detecting the level of a non-malignant disorder, a 25 hyperproliferative disorder, or a relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen in a subject, comprising: a) contacting a sample obtained from the subject with at least one binding protein described herein, at least one host cell described herein, or a population of host cells described herein; and b) detecting the level of reactivity, wherein a higher level of reactivity compared to a control level indicates the 30 level of a non-malignant disorder, a hyperproliferative disorder, or a relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen in the subject. Numerous embodiments are further provided that may be applied to any aspect encompassed by the present invention and / or combined with any other embodiment 2023204645   13 Jul 2023 described herein. For example, in one embodiment, a control level is a reference number. In another embodiment, a control level is a level of a subject without a non-malignant disorder, a hyperproliferative disorder, or a relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen. In still another aspect, a method for monitoring the progression of a non-malignant disorder, a hyperproliferative disorder, or a relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen in a subject, the method comprising: a) detecting in a subject sample at a first point in time the level of the HA-2 antigen or the cell of interest expressing HA-2, as described herein; b) repeating step a) at a subsequent point in time; and c) comparing the level of the HA-2 antigen or the cell of interest expressing HA-2 detected in steps a) and b) to monitor the progression of a non-malignant disorder, a hyperproliferative disorder, or a relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen in the subject, wherein an absent or reduced level of the HA-2 antigen or the cell of interest expressing HA-2 detected in step b) compared to step a) indicates an inhibited progression of the non-malignant disorder, the hyperproliferative disorder, or the relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen in the subject, is provided. Numerous embodiments are further provided that may be applied to any aspect encompassed by the present invention and / or combined with any other embodiment described herein. For example, in one embodiment, a subject has undergone treatment to treat the non-malignant disorder, the hyperproliferative disorder, or the relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen between the first point in time and the subsequent point in time. In yet another aspect, a method of assessing the efficacy of a therapy for a non-malignant disorder, a hyperproliferative disorder, or a relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen comprising: a) determining the presence or level of reactivity between a sample obtained from a subject and at least one binding protein described herein, at least one host cell described herein, or a population of host cells described herein, in a first sample obtained from the subject prior to providing at least a portion of the therapy for the non-malignant disorder, the hyperproliferative disorder, or the relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen to the subject, and b) determining the presence or level of reactivity between a sample obtained from the subject and at least one binding protein described 2023204645   13 Jul 2023 herein, at least one host cell described herein, or a population of host cells describged herein, in a second sample obtained from the subject following provision of the portion of the therapy for the non-malignant disorder, the hyperproliferative disorder, or the relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen, wherein the 5 absence or a reduced level of reactivity in the second sample, relative to the first sample, is an indication that the therapy is efficacious for treating the non-malignant disorder, the hyperproliferative disorder, or the relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen in the subject, is provided. Numerous embodiments are further provided that may be applied to any aspect 10 encompassed by the present invention and / or combined with any other embodiment described herein. For example, in one embodiment, a level of reactivity is indicated by a) the presence of binding and / or b) T cell activation and / or effector function, optionally wherein the T cell activation or effector function is T cell proliferation, killing, or cytokine release. In another embodiment, a T cell activation or effector function is T cell 15 proliferation, killing, or cytokine release. In still another embodiment, a T cell binding, activation, and / or effector function is detected using fluorescence activated cell sorting (FACS), enzyme linked immunosorbent assay (ELISA), radioimmune assay (RIA), immunochemically, Western blot, or intracellular flow assay. In another aspect, a method of preventing and / or treating a non-malignant disorder, 20 a hyperproliferative disorder or a relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen in a subject comprising administering to the subject a therapeutically effective amount of a composition comprising cells expressing at least one binding protein described herein. Numerous embodiments are further provided that may be applied to any aspect 25 encompassed by the present invention and / or combined with any other embodiment described herein. For example, in one embodiment, a cell is an allogeneic cell, syngeneic cell, or autologous cell. In another embodiment, a cell is genetically modified. In still another embodiment, a cell comprises a chromosomal gene knockout of a TCR gene, an HLA gene, or both a TCR gene and an HLA gene. In still another embodiment, a cell 30 comprises a knockout of an HLA gene selected from an al macroglobulin gene, a2 macroglobulin gene, a3 macroglobulin gene, pi microglobulin gene, p2 microglobulin gene, and a combination thereof. In yet another embodiment, a cell comprises a knockout of a TCR gene selected from a TCR a variable region gene, TCR P variable region gene, 2023204645   13 Jul 2023 TCR constant region gene, and combinations thereof. In another embodiment, a cell expresses CD8a and / or CD8p, optionally wherein the CD8a and / or CD8p is fused to a CD34 enrichment tag. In still another embodiment, cells are enriched using the CD34 enrichment tag. In yet another embodiment, a cell is a hematopoietic progenitor cell, 5 peripheral blood mononuclear cell (PBMC), cord blood cell, or immune cell. In another embodiment, an immune cell is a cytotoxic lymphocyte, cytotoxic lymphocyte precursor cell, cytotoxic lymphocyte progenitor cell, cytotoxic lymphocyte stem cell, CD4+ T cell, CD8+ T cell, CD4 / CD8 double negative T cell, gamma delta (y8) T cell, natural killer (NK) cell, NK-T cell, dendritic cell, or combination thereof. In another embodiment, a T cell is a 10 naive T cell, central memory T cell, effector memory T cell, or combination thereof. In still another embodiment, a T cell is a primary T cell or a cell of a T cell line. In yet another embodiment, a T cell does not express or has a lower surface expression of an endogenous TCR. In another embodiment, a cell is capable of producing a cytokine or a cytotoxic molecule when contacted with a target cell that comprises a peptide-MHC (pMHC) 15 complex comprising the HA-2 in the context of an MHC molecule. In still another embodiment, a cytokine is TNF-a, IL-2, and / or IFN-y. In yet another embodiment, a cytotoxic molecule is perforins and / or granzymes, optionally wherein the cytotoxic molecule is granzyme B. In another embodiment, a cell is capable of producing a higher level of cytokine or a cytotoxic molecule when contacted with a target cell with a 20 heterozygous expression of HA-2. In still another embodiment, a cell is capable of producing an at least 1.05-fold higher level of cytokine or a cytotoxic molecule. In yet another embodiment, a host cell is capable of killing a target cell that comprises a peptide-MHC (pMHC) complex comprising an HA-2 in the context of an MHC molecule. In another embodiment, a host cell is capable of killing a higher number of target cells when 25 contacted with target cells with a heterozygous expression of HA-2. In still another embodiment, a host cell is capable of killing an at least 1.05-fold higher number of target cells. In yet another embodiment, an HA-2 immunogenic peptide comprises the amino acid sequence YIGEVLVSV or YIGEVLVSM. In another embodiment, an MHC molecule is an MHC class I molecule. In still another embodiment, an MHC molecule comprises an 30 MHC alpha chain that is an HLA serotype HLA-A*02. In yet another embodiment, an HLA allele is selected from the group consisting of HLA-A*02:01, HLA-A*0202, HLA-A*0203, HLA-A*0205, HLA-A*0206, and HLA-A*0207 allele. In another embodiment, a target cell is a non-malignant cell or a hyperproliferating cell expressing the HA-2 antigen 2023204645   13 Jul 2023 in a subject. In still another embodiment, a composition further comprises a pharmaceutically acceptable carrier. In yet another embodiment, a composition induces an immune response against the non-malignant cells or the hyperproliferating cells expressing the HA-2 antigen in a subject. In another embodiment, a composition induces an antigen- 5 specific T cell immune response against non-malignant cells or hyperproliferating cells expressing HA-2 antigen in a subject. In still another embodiment, an antigen-specific T cell immune response comprises at least one of a CD4+ helper T lymphocyte (Th) response and a CD8+ cytotoxic T lymphocyte (CTL) response. In yet another embodiment, a hyperproliferative disorder comprises a hematological malignancy. In another 10 embodiment, a hematological malignancy comprises a leukemia, a lymphoma, a myelodysplastic disorder, a myeloproliferative neoplasm, or a myeloma. In still another embodiment, a hematological malignancy comprises a leukemia. In yet another embodiment, a leukemia is selected from acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), mixed phenotype acute leukemia (MPAL), chronic myeloid 15 leukemia (CML), B cell prolymphocytic leukemia, hairy cell leukemia, or chronic lymphocytic leukemia (CLL). In yet another embodiment, a hematological disorder comprises a lymphoma. In another embodiment, a lymphoma is selected from Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), a central nervous system lymphoma, small lymphocytic lymphoma (SLL), CD37+ dendritic cell lymphoma, lymphoplasmacytic 20 lymphoma, splenic marginal zone lymphoma, extra-nodal marginal zone B-cell lymphoma of mucosa-associated (MALT) lymphoid tissue, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, mediastinal (thymic) large B-cell lymphoma, precursor B-lymphoblastic lymphoma, immunoblastic large cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, or 25 Burkitt's lymphoma. In another embodiment, a hematological malignancy comprises a myelodysplastic disorder (MDS), optionally wherein the MDS is selected from refractory cytopenia with unilineage dysplasia (refractory anemia, refractory neutropenia, and refractory thrombocytopenia), refractory anemia with ring sideroblasts (RARS), refractory anemia with ring sideroblasts - thrombocytosis (RARS-t), refractory cytopenia with 30 multinieage dysplasia (RCMD), refractory cytopenia with multinieage dysplasia and ring sideroblasts (RCMD-RS), refractory anemia with excess blasts (RAEB), myelodysplasia unclassifiable, refractory cytopenia of childhood, or MDS with isolated del(5q). In still another embodiment, a non-malignant disorder is an immune deficiency disorder, 2023204645   13 Jul 2023 optionally wherein the immune deficiency disorder is selected from the group consisting of severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, Omenn syndrome, X-linked lymphoproliferative syndrome, chronic granulomatous disease, leukocyte adhesion deficiency, DiGeorge syndrome, and indications for hematopoietic stem cell 5 transplantation (HCT). In yet another embodiment, a non-malignant disorder is a non-malignant hematology disorder, optionally wherein the non-malignant hematology disorder is selected from the group consisting of sickle cell anemia, thalassemia, aplastic anemia, hemophagocytic lymphohistiocytosis (HLH), severe aplastic anemia, marrow failure syndromes, Fanconi anemia, Diamond-Blackfan anemia, and Shwachman Diamond 10 syndrome. In another embodiment, a non-malignant disorder is an autoimmune disorder, optionally wherein the autoimmune disorder is systemic sclerosis or multiple sclerosis. In still another embodiment, a subject is receiving or previously received a hematopoietic cell transplant (HCT), optionally wherein the HCT comprises cells that do not express HA-2 antigen, are not recognized by a binding protein described herein, are not of serotype HLA- 15   A*02, and / or do not express an HLA-A*02:01 allele. In yet another embodiment, an HCT comprises a donor hematopoeitic cell comprising a chromosomal knockout of a gene that encodes an HLA component, a chromosomal knockout of a gene that encodes a TCR component, or both. In another embodiment, a subject had previously received lymphodepleting chemotherapy. In still another embodiment, a lymphodepleting 20 chemotherapy comprised cyclophosphamide, fludarabine, anti-thymocyte globulin, or a combination thereof. In yet another embodiment, a method further comprises administering at least one additional treatment for the non-malignant disorder, the hyperproliferative disorder or the relapse of a hyperproliferative disorder to a subject. In another embodiment, at least one additional treatment for the non-malignant disorder, the hyperproliferative 25 disorder or the relapse of a hyperproliferative disorder is administered concurrently or sequentially with the composition. In still another embodiment, a subject is an animal model of disorder characterized by HA-2 antigen and / or the subject is a mammal, optionally wherein the mammal is a human, a primate, or a rodent. In still another aspect, an expression vector comprising a promoter operably linked 30 to a nucleic acid sequence encoding CD8a and / or CD8p, is provided. Numerous embodiments are further provided that may be applied to any aspect encompassed by the present invention and / or combined with any other embodiment described herein. For example, in one embodiment, a nucleic acid sequence encoding 2023204645   13 Jul 2023 CD8a or CD8P is operably linked to a nucleic acid encoding a tag such that the tag is fused to the CD8a or CD8p. In another embodiment, a nucleic acid encoding a tag is at the 5’ upstream of the nucleic acid sequence encoding CD8a or CD8p such that the tag is fused to the N-terminal of CD8a or CD8p. In still another embodiment, a tag is a CD34 enrichment 5 tag. In yet another embodiment, a vector further comprises a nucleic sequence encoding a TCRa and / or TCRp. In another embodiment, a TCRa and / or TCRp comprises a mutated transmembrane domain and / or a mutated constant domain. In still another embodiment, a mutated transmembrane domain and / or mutated constant domain enhance cellular surface expression of TCRa and / or TCRp while decreasing expression of endogenous TCRa 10 and / or TCRp. In yet another embodiment, a nucleic acid sequence encoding CD8a and / or CD8P and the nucleic sequence encoding TCRa and / TCRp, are interconnected with an internal ribosome entry site or a nucleic acid sequence encoding a self-cleaving peptide. In another embodiment, a self-cleaving peptide is P2A, E2A, F2A or T2A. In still another embodiment, a vector further comprises a nucleic sequence encoding a polypeptide selected 15 from the group consisting of polypeptide sequences listed in Table 1, or a sequence with at least about 80% homology to a nucleic acid encoding a polypeptide selected from the group consisting of the polypeptide sequences listed in Table 1, optionally wherein the isolated nucleic acid molecule comprises 1) a TRAV, TRAJ, and / or TRAC gene or fragment thereof selected from the group of TRAV, TRAJ, and TRAC genes listed in Table 1 and / or 2) a 20 TRBV, TRBJ, and / or TRBC gene or fragment thereof selected from the group of TRBV, TRBJ, and TRBC genes listed in Table 1. In yet another embodiment, a vector has a nucleic sequence set forth in Table 2. Brief Description of the Drawings 25         Figure 1 shows a schematic diagram of TCR discovery platform. The TCR discovery platform identified 1,302 novel HA-2 TCRs. CD14+ monocytes were isolated from PBMCs of six HA-2 negative healthy donors on day -4 and differentiated to mature DCs. On day -1, naive CD8 T cells were isolated from autologous PBMCs and rested overnight. Co-culture of CD8 T cells and DCs was performed following 3 h pulsing of 30 DCs with 1 pg / mL HA-2 REF peptide (YIGEVLVSV), followed by an 11-day cell expansion phase. Dextramer staining was performed with A*02:01-specific HA-2 REF (YIGEVLVSV) and HA-2 SNP (YIGEVLVSM) dextramers to identify clones, which were then sorted for single cell TCR sequencing. 2023204645   13 Jul 2023 Figure 2 shows results of a DexScan performed on 380 TCRs identified as shown in Figure 1 for functional assessment using a library of individually cloned HA-2 TCR viruses. Briefly, pan T cells isolated from HLA-A*01:01 / A*03:01-positive healthy donor PBMCs were transduced to express a pool of HA-2-specific TCRs and stained with various 5   dilutions of A*02:01 -specific HA-2 REF (YIGEVLVSV) dextramer. Dextramer-bound cells were sorted and sequenced. TCR enrichment (i.e., change in the proportion of TCR in sorted samples versus input) was used to nominate TCRs for functional evaluation. The figure indicates TCRs selected by DexScan for advancement into functional evaluation. Figure 3 shows that HA-2 TCRs are expressed on the surface of engineered T cells. 10 Pan-T cells were transduced to express 15 HA-2-specific TCRs that were selected from the DexScan screen. Dot plots show surface expression of the TCRs as assessed by A*02:01-specific HA-2 REF (YIGEVLVSV) dextramer staining. Figure 4A - Figure 4D show HA-2 TCR functional evaluation results. Pan T cells isolated from HLA-A*01:01 / A*03:01-positive healthy donor PBMCs were transduced to 15 express HA-2-specific TCRs, and assessed for functional responses to target cells expressing HA-2 and HLA-A*02:01. Figure 4A shows dot plots demonstrating representative expression of three HA-2-specific TCRs as assessed by A*02:01 -specific HA-2 REF (YIGEVLVSV) dextramer staining. Figure 4B - Figure 4D show functional responses of HA2-specific TCRs to HLA-A*02:01+ HA-2+ target cell lines, DEL (high 20 MHC, high HA-2), THP-1 (medium MHC, low HA-2), TF-1 (low MHC, low HA-2), and a negative control cell line, NB4 (irrelevant MHC). Figure 4B shows results of engineered T cells co-cultured with IncuCyte® NucLight™ Red-labeled target cell lines at indicated E:T ratios. Cell survival was quantified on an IncuCyte® machine as a readout of cytotoxicity of the T cells. Figure 4C shows production of IFN-y, IL-2, TNF-a and granzyme B in co-25 culture supernatants at 24 h (E:T 1:1). AT cell-only condition was used to determine background level of cytokine production. The dotted line represents the highest levels of cytokine in the T cell-only condition. Figure 4D shows proliferation of the HA-2-specific TCR-expressing T cells. Engineered T cells were labeled with a proliferation dye and cocultured with target cell lines for 96 h (E:T 1:1). Dye dilution was used to assess 30 proliferation of CD8+ and CD4+ T cells. Counting beads were added to the samples prior to analysis by flow cytometry and absolute numbers of divided CD8+ and CD4+ T cells were enumerated. A T cell-only condition was used to determine background level of proliferation. The dotted line represents the highest levels of proliferation in T cell only 2023204645   13 Jul 2023 condition. TCRs were compared by one-way ANOVA followed by Tukey’s multiple comparison test. * P<0.05, ** P<0.005, *** P<0.0005, **** P<0.0001. These experiments were performed in 2-3 donors and representative data from 1 donor is shown. Figure 5 shows alloreactivity landscape results for MJ2-DP8 and MJ7-DP19 TCRs 5 tested in an alloreactivity assay. Endogenous MHCs were knocked out of HEK293T cells using CRISPR / Cas9-gRNA ribonucleoprotein delivery. MHC-null HEK293T cells were transduced with IncuCyte® NucLight™ Red and individual MHCs representing the 110 most prevalent HLA types using lentiviral transduction. A cell line that stably expresses A*02:01 and a 90-residue protein fragment that includes the HA-2 REF (YIGEVLVSV) 10 sequence was used as a positive control. Cells in 96-well format were incubated with human primary CD8+ T cells expressing MJ2-DP8 and MJ7-DP19 TCRs for 48 h. Target cell numbers were measured over time using an IncuCyte® machine by measuring the number of IncuCyte® NucLight™ Red-positive cells. Cell inhibition at 48 h of each TCR on each MHC in the assay was calculated as 1- (Target cell doubling[Incubated with TCR- 15 expressing T cells] / Target cell doubling[Incubated with T cell media]). To subtract the effect of non-MHC-related target cell growth inhibition such as competition for nutrition from T cells or non-specific cell killing from donor T cells and to correct for batch effect of each 96-well plate, the cell inhibition value of each well (each MHC) on each 96-well plate were subtracted by the median of cell inhibition of the wells on each 96-well plate. 20          Figure 6 shows results of a DexScan performed on 1,174 TCRs identified as shown in Figure 1 for functional assessment using a library pool of HA-2 TCR viruses. Briefly, pan T cells isolated from HLA-A*01:01 / A*03:01-positive healthy donor PBMCs were transduced with a library pool of HA-2 TCR viruses and stained A*02:01 -specific HA-2 REF (YIGEVLVSV) dextramer. Dextramer-bound cells were sorted and sequenced. TCR 25 enrichment (i.e., change in the proportion of TCR in sorted samples versus input) was used to nominate TCRs for functional evaluation. The figure indicates TCRs selected by DexScan for advancement into functional evaluation. Figure 7A - Figure 7M show HA-2 TCR functional evaluation results shown using mean with standard error of the mean (SEM) indications. Pan T cells isolated from HLA-30   A*01:01 / A*03:01-positive healthy donor PBMCs were transduced to express HA-2- specific TCRs, and assessed for functional responses to target cells expressing HA-2 and HLA-A*02:01. Figure 7A shows dot plots demonstrating representative expression of fifteen HA-2-specific TCRs as assessed by A*02:01 -specific HA-2 REF (YIGEVLVSV) 2023204645   13 Jul 2023 dextramer staining. Figure 7B - Figure 7M show functional responses of HA2-specific TCRs to the followng HLA-A*02:01+ HA-2+ target cell lines: DEL (high MHC, high HA-2) (Figure 7B - Figure 7D), THP-1 (medium MHC, low HA-2) (Figure 7E - Figure 7G), TF1 (low MHC, low HA-2) (Figure 7H - Figure 7J), and the negative control cell line, NB4 5 (irrelevant MHC) (Figure 7K - Figure 7M). Engineered T cells were co-cultured with IncuCyte® NucLight™ Red-labeled target cell lines at indicated E:T ratios, and their survival was quantified on an IncuCyte® machine as a readout of cytotoxicity of the T cells. Production of IFN-y, IL-2, TNF-a and granzyme B in co-culture supernatants at 24 h (E:T 1:1). AT cell-only condition was used to determine background level of cytokine 10 production. The dotted line represents the highest levels of cytokine in the T cell-only condition. To determine proliferation of the HA-2-specific TCR-expressing T cells, engineered T cells were labeled with a proliferation dye and co-cultured with target cell lines for 96 h (E:T 1:1). Dye dilution was used to assess proliferation of CD8+ and CD4+ T cells. Counting beads were added to the samples prior to analysis by flow cytometry and 15 absolute numbers of divided CD8+ and CD4+ T cells were enumerated. A T cell-only condition was used to determine background level of proliferation. As described above, the dotted line represents the highest levels of proliferation in T cell-only condition. TCRs were compared by one-way ANOVA followed by Tukey’s multiple comparison test. P<0.05 indicates statistical significance and key statistics are reported with each figure as 20 follows: a) the left panel bar graph of Figure 7B shows that the results for each of MJ2- DP22, MJ9-DP5, and MJ7-DP19 were significantly different from the results for each of MJ14-SP4, MJ13-SP43, MJ14-DP162, and NTD (P<0.05); b) the right panel bar graph of Figure 7B shows that the results for each of MJ14-DP317, MJ2-DP8, and MJ7-DP19 were significantly different from the results for each of MJ14-DP33, MJ13-DP32, and NTD 25   (P<0.05); c) the interferon-y bar graph of Figure 7C shows that the results for each of MJ2- DP22, MJ14-DP317, and MJ2-DP8 were significantly different from the results for each of MJ14-SP4, MJ13-SP43, MJ14-DP137, MJ14-DP162, MJ14-DP33, MJ2-DP24, MJ13-DPI48, MJ13-DP32, and NTD (PO.05), while the results for each of MJ9-DP5 and MJ7-DPI9 were significantly different from the results for each of all TCRs, except MJ 14 30   DP137 (P<0.05); d) the IL-2 and TNF-a bar graphs of Figure 7C show that the results for each of MJ2-DP22, MJ9-DP5, MJ14-DP317, MJ2-DP8, and MJ7-DP19 were significantly different from the results for each of MJ14-SP4, MJ13-SP43, MJ14-DP137, MJ14-DP162, MJ14-DP33, MJ2-DP24, MJ13-DP148, MJ13-DP32, and NTD (P<0.05); e) the granzyme 2023204645   13 Jul 2023 B bar graph of Figure 7C shows that the results for each of MJ2-DP22, MJ14-DP317, MJ2-DP8, and MJ7-DP19 were significantly different from the results for each of MJ14-SP4, MJ13-SP43, MJ14-DP137, MJ14-DP162, MJ14-DP33, MJ2-DP24, MJ13-DP148, MJ13-DP32, and NTD (P<0.05), while the result for MJ9-DP5 was significantly different from 5 the result for each of all TCRs, except MJ14-DP137 (P<0.05); f) the CD8 T cell proliferation bar graph of Figure 7D shows that the results for each of MJ14-DP317, MJ9-DP5, MJ2-DP8, and MJ7-DP19 were significantly different from the results for each of MJ14-SP4, MJ13-SP43, MJ14-DP137, MJ14-DP162, MJ14-DP33, MJ2-DP24, MJ13-DP148, MJ13-DP32, and NTD (P<0.05), while the result for MJ2-DP22 was significantly 10   different from the results for each of all TCRs, except MJ14-DP137; g) the CD4 T cell proliferation bar graph of Figure 7D shows that the results for each of MJ14-DP317 and MJ2-DP8 were significantly different from the results for each of MJ14-SP4, MJ13-SP43, MJ14-DP137, MJ14-DP162, MJ14-DP33, MJ2-DP24, MJ13-DP148, MJ13-DP32, and NTD (P<0.05), while the results for each of MJ2-DP22, MJ9-DP5, and MJ7-DP19 were 15 significantly different from the results for each of all TCRs, except MJ14-DP137 (P<0.05); h) the left panel bar graph of Figure 7E shows that the results for each of MJ2-DP22, MJ9-DP5, and MJ7-DP19 were significantly different from the results for each of MJ14-SP4, MJ13-SP43, MJ14-DP137, MJ14-DP162, and NTD (P<0.05); i) the right panel bar graph of Figure 7E shows that the results for each of MJ14-DP317, MJ2-DP8, and MJ7-DP19 were 20 significantly different from the results for each of MJ14-DP33, MJ12-DP24, MJ13-DP148, MJ13-DP32, and NTD (P<0.05); j) the interferon-y, TNF-a and granzyme B bar graphs of Figure 7F show that the results for each of MJ2-DP22, MJ9-DP5, MJ14-DP317, MJ2-DP8, and MJ7-DP19 were significantly different from the results for each of MJ14-SP4, MJ13-SP43, MJ14-DP137, MJ14-DP162, MJ14-DP33, MJ2-DP24, MJ13-DP148, MJ13-DP32, 25 and NTD (P<0.05) and only MJ9-DP5, MJ14-DP317, and MJ2-DP8 produced IL-2 above background levels; k) the CD8 T cell proliferation graph and CD4 T cell proliferation graph of Figure 7G each show that the results for each of MJ2-DP22, MJ14-DP317, MJ9-DP5, MJ2-DP8, and MJ7-DP19 were significantly different from the results for MJ14-SP4, MJ13-SP43, MJ14-DP137, MJ14-DP162, MJ14-DP33, MJ2-DP24, MJ13-DP148, MJ13- 30   DP32, and NTD (P<0.05); 1) the left panel bar graph of Figure 7H shows that the results for each of MJ2-DP22, MJ9-DP5, and MJ7-DP19 were significantly different from the results for each of MJ14-SP4, MJ13-SP43, MJ14-DP137, MJ14-DP162, and NTD (P<0.05); and m) the right panel bar graph of Figure 7H shows that the results for each of MJ14-DP317, 2023204645   13 Jul 2023 MJ2-DP8, and MJ7-DP19 were significantly different from the results for each of MH 4-DP33, MJ12-DP24, MJ13-DP148, MJ13-DP32, and NTD (P<0.05). Figure 8A - Figure 8M similarly show HA-2 TCR functional evaluation results for seven HA-2 TCRs in two unique donors selected based on data from Figure 7A - Figure 5   7M. Bar graphs indicate mean with standard error of the mean (SEM). Pan T cells isolated from HLA-A*01:01 / A*03:01-positive healthy donor PBMCs were transduced to express HA-2-specific TCRs, and assessed for functional responses to target cells expressing HA-2 and HLA-A*02:01. Figure 8A shows dot plots demonstrating expression of seven HA-2-specific TCRs as assessed by A*02:01-specific HA-2 REF (YIGEVLVSV) dextramer 10 staining in two unique donors. Figure 8B - Figure 8M show functional responses of the HA2-specific TCRs to the following HLA-A*02:01+ HA-2+ target cell lines: DEL (high MHC, high HA-2) (Figure 8B - Figure 8D), THP-1 (medium MHC, low HA-2) (Figure 8E -Figure 8G), TF1 (low MHC, low HA-2) (Figure 8H - Figure 8J), and the negative control cell line, NB4 (irrelevant MHC; HLA-A*02:01- (i.e., negative)) (Figure 8K - Figure 8M). 15 Engineered T cells were co-cultured with IncuCyte® NucLight™ Red-labeled target cell lines at indicated E:T ratios, and their survival was quantified on an IncuCyte® machine as a readout of cytotoxicity of the T cells. Production of IFN-y, IL-2, TNF-a and granzyme B in co-culture supernatants at 24 h (E:T 1:1). AT cell-only condition was used to determine background level of cytokine production. The dotted line represents the highest levels of 20 cytokine in the T cell-only condition. To determine proliferation of the HA-2-specific TCR-expressing T cells, engineered T cells were labeled with a proliferation dye and cocultured with target cell lines for 96 h (E:T 1:1). Dye dilution was used to assess proliferation of CD8+ and CD4+ T cells. Counting beads were added to the samples prior to analysis by flow cytometry and absolute numbers of divided CD8+ and CD4+ T cells were 25 enumerated. A T cell-only condition was used to determine background level of proliferation. As described above, the dotted line represents the highest levels of proliferation in the T cell-only condition. TCRs were compared by one-way ANOVA followed by Tukey’s multiple comparison test. P<0.05 indicates statistical significance and key statistics are reported with each figure as follows: a) the left panel and right panel bar 30 graphs of Figure 8B show that the results for each of MJ14-DP317, MJ9-DP5, MJ2-DP22, MJ7-DP19, and MJ2-DP8 were significantly different from the results for each of MJ14-SP4 and NTD (P<0.05); b) bar graphs of Figure 8C show that results for each of MJ14-DP317, MJ9-DP5, MJ2-DP22, MJ7-DP19, and MJ2-DP8 were significantly different from 2023204645   13 Jul 2023 the results for each of MJ14-DP137, MJ14-SP4, and NTD for all cytokines in both donors (P<0.05), except that only the result for MJ14-DP317 was not different from the result for MJ14-DP137 for TNF-a in donor 3; c) the CD8 T cell proliferation panel for donor 2 of Figure 8D shows that the results for each of MJ14-DP317, MJ9-DP5, and MJ2-DP22 were 5 significantly different from the results for each of MJ14-SP4 and NTD (P<0.05), while the results for each of MJ7-DP19 and MJ2-DP8 were significantly different from the results for each of MJ14-DP137, MJ14-SP4, and NTD (P<0.05); d) the CD4 T cell proliferation panel for donor 2 of Figure 8D shows that the results for each of MJ14-DP317, MJ2-DP22, MJ7-DP19, and MJ2-DP8 were significantly different from the results for each of MJ14-DP137, 10   MJ14-SP4, and NTD (P<0.05), while the result for MJ9-DP5 was significantly different from the results for each of MJ14-SP4 and NTD (P<0.05); e) the CD8 T cell proliferation panel and the CD4 T cell proliferation panel for donor 3 of Figure 8D each shows that the results for each of MJ14-DP317, MJ9-DP5, MJ2-DP22, MJ7-DP19, and MJ2-DP8 were significantly different from the results for each of MJ14-DP137, MJ14-SP4, and NTD 15   (P<0.05); f) the left panel and right panel bar graphs of Figure 8E show that the results for each of MJ14-DP317, MJ9-DP5, MJ2-DP22, MJ7-DP19, and MJ2-DP8 were significantly different from the results for each of MJ14-DP137, MJ14-SP4, and NTD for each donor (P<0.05); g) bar graphs of Figure 8F show that results for each of MJ14-DP317, MJ9-DP5, MJ2-DP22, MJ7-DP19, and MJ2-DP8 were significantly different from the results for each 20 of MJ14-DP137, MJ14-SP4, and NTD for IFN-y, IL-2 and TNF-a in both donors (P<0.05), the results for each of MJ14-DP317, MJ9-DP5, MJ7-DP19, and MJ2-DP8 were significantly different from the results for each of MJ14-DP137, MJ14-SP4, and NTD in donor 2 for granzyme B (P<0.05), and the results for each of MJ9-DP5, MJ7-DP19, and MJ2-DP8 were significantly different from the results for each of MJ14-DP137, MJ14-SP4, 25 and NTD in donor 3 for granzyme B (P<0.05); h) bar graphs of Figure 8G show that the results for each of MJ14-DP317, MJ9-DP5, MJ2-DP22, MJ7-DP19, and MJ2-DP8 were significantly different from the results for each of MJ14-DP137, MJ14-SP4, and NTD for each of CD8 T cell proflieration and CD4 T cell proliferation for both donors (P<0.05); i) the bar graph for donor 2 of Figure 8H shows that the results for each of MJ14-DP317, 30 MJ9-DP5, MJ2-DP22, MJ7-DP19, and MJ2-DP8 were significantly different from the results for each of MJ14-DP137, MJ14-SP4, and NTD (P<0.05); j) the bar graph for donor 3 of Figure 8H shows that the results for each of MJ9-DP5, MJ7-DP19, and MJ2-DP8 were significantly different from the results for each of MJ14-DP137, MJ14-SP4, and NTD 2023204645   13 Jul 2023 (P<0.05), while the result for MJ2-DP22 was significantly different from the results for each of MJ14-DP137 and NTD (P<0.05); k) the CD8 T cell proliferation bar graph for donor 2 of Figure 8J shows that the results for each of MJ14-DP317, MJ9-DP5, MJ2-DP22, MJ7-DP19, and MJ2-DP8 were significantly different from the results for each of MJ14-5   DP137, MJ14-SP4, and NTD (P<0.05), while the CD4 T cell proliferation bar graph for donor 2 of Figure 8J di not show significant differences between the TCRs; and 1) the CD8 T cell proliferation and the CD4 T cell proliferation bar graphs for donor 3 of Figure 8J each show that the result for MJ2-DP8 was significantly different from each of the results for MJ14-DP137, MJ14-SP4, and NTD (P<0.05) and that the result for MJ2-DP22 was 10 significantly different from each of the results for MJ14-DP137 and NTD (P<0.05). Figure 9 shows alloreactivity landscape results for MJ9-DP5, MJ2-DP22, and MJ14-DP317 tested in an alloreactivity assay. Endogenous MHCs were knocked out of HEK293T cells using CRISPR / Cas9-gRNA ribonucleoprotein delivery. MHC-null HEK293T cells were transduced with IncuCyte® NucLight™ Red and individual MHCs 15 representing the 110 most prevalent HLA types using lentiviral transduction. A cell line was prepared that stably expresses A*02:01 and a 90-residue protein fragment that includes the HA-2 REF (YIGEVLVSV) as positive control. Cells in 384-well format were incubated with human primary CD8+ T cells expressing MJ9-DP5, MJ2-DP22, and MJ14-DP317 for 48 h. Target cell numbers were measured over time using IncuCyte® machine by 20 measuring the number of IncuCyte® NucLight™ Red positive cells. Cell inhibition at 48 h of each TCR on each MHC in the assay was calculated as 1- (Target cell doubling[Incubated with TCR-expressing T cells] / Target cell doubling[Incubated with untransduced donor T cells]). To correct for batch effect of each 384-well plate, the cell inhibition value of each well (each MHC) on each 384-well plate were subtracted by the 25 median of cell inhibition of the wells on each 384-well plate. Figure 10A and Figure 10B show strategies for conducting and results from off-target screen assays. Figure 10A shows a schematic overview of the genome-wide safety screen assay used. In this genome-wide safety screen, T cells expressing HA2-MJ14-DP317 were co-cultured with a library of HLA-A*02:01+ target cells, wherein each such 30 target cell expresses a different 90-amino acid (90-aa) protein fragment. Collectively, the library includes fragments that tile across every protein in 22-amino acid steps. Fragments are processed naturally by the target cells and the resulting peptides are displayed on cellsurface MHCs. If a T cell recognizes its target, it attempts to kill the target cell, thereby 2023204645   13 Jul 2023 activating a fluorescent reporter. By isolating fluorescent cells and sequencing their expression cassettes, the natural target(s) of the TCR are revealed. The screen is designed to overpredict off-targets by overexpressing 90-aa protein fragments, which are more efficiently processed than full-length proteins, such that identified hits may not be expected 5 to be physiologically relevant off-targets. Kula et al. (2019) Cell 178:1016-1028 provide additional details. Figure 10B shows that multiple tiles containing the HA-2 epitope were significantly enriched in the screens with HA2-MJ14-DP317 (TCR-101) and further shows that multiple genes were identified as potential off-targets. The x-axis represents protein fragments in the peptidome library and the Y-axis represents fold enrichment of individual 10 tiles over input library. Figure 11A and Figure 11B show that TSC-101 displays as least 100-3,000 fold lower affinity for putative off-target peptides as compared to target HA-2 peptide. The cytotoxic activity of TSC-101 TCR-T cells was tested against T2 cells pulsed with different on- and off-target peptides. Figure 11A shows that affinity of TCR-101 for on- and off-15 target peptides was measured by calculating area under the curve (AUC) for growth of the T2 target cells co-cultured with TSC-101 T cells was measured over 72h as a function of the dose of peptide. Figure 10B shows individual ECso for the 8-point titration of the HA-2+peptide, HA-2- peptide, putative off-target MY03A / B peptide, putative off-target MALT1 peptide. Note that the determination of EC50 for the remaining peptides (MTA1, 20 KLHL30 and HUWE1) is not displayed as their 3-point titration did not enable the calculation of the ECso. Figure 12A and Figure 12B show that TSC-101 exhibits robust cytotoxicity against primary hematologic tumor samples, including acute myeloid leukemia (AML) and acute lympocytic leukemia (ALL) tumor samples. TSC-101 and non-engineered control (NC) T 25 cells were co-cultured for 20 h with HLA-A*02:01-positive PBMCs or BMMCs from AML (Figure 12A) or ALL (Figure 12B) patients at an E:T of 10:1. The viability of targets upon co-culture with TSC-101 T cells was then assessed by flow cytometry and normalized to the viability of targets upon co-culture with NC T cells. Data are representative of 3 donors. 30          Figure 13 provides summary data. Figure 14A and Figure 14B show that TSC-101 lacks reactivity to non-hematopoietic primary human cells. The data show IFN-y concentrations measured in the supernatant of TSC-101 co-cultured during 48 h with different target cells corrected for 2023204645   13 Jul 2023 background (background IFN-y was measured with effector cells alone (Figure 14A). Target cells included NB-4 (negative control) and THP-1 (positive control) and HLA-A*02:01 positive primary human cells, including PBMCs (green bars), endothelial cells (HUVEC), skeletal muscle cells (SKMC), keratinocytes (NHEK), bronchial epithelial cells 5 (HBEC), melanocytes (NHEM), retina pigmented epithelial cells (RPEC) small intestine epithelial cells (SIEC), Gaba neurons, hepatocytes, gastric epithelial cells (GEC), astrocytes, cardiomyocytes (HCM), cardiac fibroblasts (HCF), dermal fibroblasts (HDF), and pulmonary fibroblasts (HPF). Each run of co-culture is presented and separated by a dashed line. The non-hematopoietic were pulsed with 100 ng / mL of HA-2+ peptide prior to 10 the co-culture (Figure 14B). Detailed Description of the Invention The present invention is based, at least in part, on the discovery of binding proteins, including T cell receptors (TCRs), that recognize HA-2 antigen (e.g., immunogenic peptide 15 comprising the amino acid sequence YIGEVLVSV or YIGEVLVSM). Accordingly, the present invention relates, in part, to the identified binding proteins (e.g., TCRs), host cells expressing binding proteins (e.g., TCRs), compositions comprising binding proteins (e.g., TCRs) and host cells expressing binding proteins (e.g., TCRs), methods of diagnosing, prognosing, and monitoring T cell response to cells expressing the 20 HA-2 antigen, and methods for preventing and / or treating a non-malignant disorder, a hyperproliferative disorder, or a relapse of a hyperproliferative disorder characterized by expression of the HA-2 antigen by administering host cells expressing binding proteins (e.g., TCRs). 25 I. Definitions For convenience, certain terms employed in the specification, examples, and appended claims are collected here. The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” 30 means one element or more than one element. The term “administering" means providing a pharmaceutical agent or composition to a subject, and includes, but is not limited to, administering by a medical professional and self-administering. This involves the physical introduction of a composition comprising a 2023204645   13 Jul 2023 therapeutic agent to a subject, using any of the various methods and delivery systems known to those skilled in the art. In some embodiments, routes of administration for binding proteins described herein include intravenous, intraperitoneal, intramuscular, subcutaneous, spinal or other parenteral routes of administration, for example by injection 5 or infusion. The phrase "parenteral administration" as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intraperitoneal, intramuscular, intraarterial, intrathecal, intralymphatic, intralesional, intracapsular, intraorbital, intracardiac, intradermal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, 10 subarachnoid, intraspinal, epidural and intrasternal injection and infusion, as well as in vivo electroporation. Alternatively, a binding protein described herein may be administered via a non-parenteral route, such as a topical, epidermal or mucosal route of administration, for example, intranasally, orally, vaginally, rectally, sublingually or topically. Administering may also be performed, for example, once, a plurality of times, and / or over one or more 15 extended periods. As used herein, the term “antigen” refers to any natural or synthetic immunogenic substance, such as a protein, peptide, or hapten. An antigen may be an HA-2antigen, or a fragment thereof, against which protective or therapeutic immune responses are desired. The term “adjuvant” as used herein refers to substances, which when administered 20 prior, together or after administration of an antigen accelerates, prolong and / or enhances the quality and / or strength of an immune response to the antigen in comparison to the administration of the antigen alone. Adjuvants can increase the magnitude and duration of the immune response induced by vaccination. The term “antibody” as used to herein includes whole antibodies and any antigen 25 binding fragments (i.e., “antigen-binding portions”) or single chains thereof. An “antibody” refers, in one embodiment, to a glycoprotein comprising at least two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds, or an antigen binding portion thereof. Each heavy chain is comprised of a heavy chain variable region (abbreviated herein as Vh) and a heavy chain constant region. In certain naturally occurring 30 antibodies, the heavy chain constant region is comprised of three domains, CHI, CH2 and CH3. In certain naturally occurring antibodies, each light chain is comprised of a light chain variable region (abbreviated herein as Vl) and a light chain constant region. The light chain constant region is comprised of one domain, CL. The Vh and Vl regions may be 2023204645   13 Jul 2023 further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR). Each Vh and Vl is composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, 5 FR3, CDR3, FR4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The constant regions of the antibodies may mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (Clq) of the classical complement system. 10          The term “antigen presenting cell” or "APC" includes professional antigen presenting cells (e.g., B lymphocytes, monocytes, dendritic cells, Langerhans cells), as well as other antigen presenting cells (e.g., keratinocytes, endothelial cells, astrocytes, fibroblasts, and oligodendrocytes). The term “antigen-binding portion” of a binding protein, such as a TCR, as used 15 herein, refers to one or more portions of a TCR that retain the ability to bind (e.g., specifically and / or selectively) to an antigen (e.g., an HA-2 antigen). Such portions are, for example, between about 8 and about 1500 amino acids in length, suitably between about 8 and about 745 amino acids in length, suitably about 8 to about 300, for example about 8 to about 200 amino acids, or about 10 to about 50 or 100 amino acids in length. It has been 20 shown that the antigen-binding function of a TCR can be performed by fragments of a fulllength TCR. Examples of binding portions encompassed within the term “antigen-binding portion” of a TCR, include (i) a Fv fragment consisting of the Va and Vp domains of a TCR, (ii) an isolated complementarity determining region (CDR) or (iii) a combination of two or more isolated CDRs which may optionally be joined by a synthetic linker. 25 Furthermore, although Va and Vp, are coded by separate genes, they may be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the Va and Vp regions pair to form monovalent molecules (known as single chain TCR (scTCR)). Such single chain TCRs are also intended to be encompassed within the term “antigen-binding portion” of a TCR. These TCR fragments can be obtained using 30 conventional techniques known to those with skill in the art, and the fragments are screened for utility in the same manner as are complete binding proteins. Antigen-binding portions may be produced by recombinant DNA techniques, or by enzymatic or chemical cleavage of intact immunoglobulins. 2023204645   13 Jul 2023 The terms "complementarity determining region" and "CDR" are synonymous with "hypervariable region" or "HVR" and are known in the art to refer to non-contiguous sequences of amino acids within certain binding proteins, such as TCR variable regions, which confer antigen specificity and / or binding affinity. For TCRs, in general, there are 5 three CDRs in each a-chain variable region (aCDRl, aCDR2, and aCDR3) and three CDRs in each p-chain variable region (PCDR1, PCDR2, and PCDR3). CDR3 is believed to be the main CDR responsible for recognizing processed antigen. CDR1 and CDR2 mainly interact with the MHC. The term “body fluid” refers to fluids that are excreted or secreted from the body as 10 well as fluids that are normally not excreted or secreted from the body (e.g., amniotic fluid, aqueous humor, bile, blood and blood plasma, cerebrospinal fluid, cerumen and earwax, cowper’s fluid or pre-ejaculatory fluid, chyle, chyme, stool, female ejaculate, interstitial fluid, intracellular fluid, lymph, menses, breast milk, mucus, pleural fluid, pus, saliva, sebum, semen, serum, sweat, synovial fluid, tears, urine, vaginal lubrication, vitreous 15 humor, vomit). In some embodiments, the body fluid comprises immune cells, optionally wherein the immune cells are cytotoxic lymphocytes such as cytotoxic T cells and / or NK cells, CD4+ T cells, and the like. The term “coding region” refers to regions of a nucleotide sequence comprising codons that are translated into amino acid residues, whereas the term “non-coding region” 20 refers to regions of a nucleotide sequence that are not translated into amino acids (e.g., 5' and 3' untranslated regions). The term “complementary” refers to the broad concept of sequence complementarity between regions of two nucleic acid strands or between two regions of the same nucleic acid strand. It is known that an adenine residue of a first nucleic acid region 25 is capable of forming specific hydrogen bonds (“base pairing”) with a residue of a second nucleic acid region which is anti-parallel to the first region if the residue is thymine or uracil. Similarly, it is known that a cytosine residue of a first nucleic acid strand is capable of base pairing with a residue of a second nucleic acid strand which is anti-parallel to the first strand if the residue is guanine. A first region of a nucleic acid is complementary to a 30 second region of the same or a different nucleic acid if, when the two regions are arranged in an antiparallel fashion, at least one nucleotide residue of the first region is capable of base pairing with a residue of the second region. In some embodiments, the first region comprises a first portion and the second region comprises a second portion, whereby, when 2023204645   13 Jul 2023 the first and second portions are arranged in an antiparallel fashion, at least about 50%, and, in other embodiments, at least about 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more, or any range in between, inclusive, such as at least about 80%-100%, of the 5 nucleotide residues of the first portion are capable of base pairing with nucleotide residues in the second portion. In some embodiments, all nucleotide residues of the first portion are capable of base pairing with nucleotide residues in the second portion. As used herein, the term “costimulate” with reference to activated immune cells includes the ability of a costimulatory molecule to provide a second, non-activating 10 receptor mediated signal (a “costimulatory signal”) that induces proliferation or effector function. For example, a costimulatory signal may result in cytokine secretion, e.g., in a T cell that has received a T cell-receptor-mediated signal. Immune cells that have received a cell-receptor mediated signal, e.g., via an activating receptor are referred to herein as “activated immune cells.” 15          "CD3" is known in the art as a multi-protein complex of six chains (see, Abbas and Lichtman, Cellular and Molecular Immunology (9th Edition) (2018); Janeway et al. (Immunobiology) (9th Edition) (2016)). In mammals, the complex comprises a CD3y chain, a CD38 chain, two CD3e chains, and a homodimer of CD3£ chains. The CD3y, CD36, and CD3e chains are related cell surface proteins of the immunoglobulin superfamily containing 20 a single immunoglobulin domain. The transmembrane regions of the CD3y, CD38, and CD3e chains are negatively charged, which is a characteristic that is believed to allow these chains to associate with positively charged regions or residues of T cell receptor chains. The intracellular tails of the CD3y, CD35, and CD3s chains each contain a single conserved motif known as an immunoreceptor tyrosine-based activation motif or IT AM, whereas 25 each CD3^ chain has three ITAMs. Without wishing to be bound by theory, it is believed that the IT AMs are important for the signaling capacity of a TCR complex. CD3 used in accordance with the present invention may be from various animal species, including human, mouse, rat, or other mammals. A "component of a TCR complex," as used herein, refers to a TCR chain (i.e ., 30 TCRa, TCRp, TCRy or TCR8), a CD3 chain (i.e., CD3y, CD38, CD3e or CD3Q, or a complex formed by two or more TCR chains or CD3 chains (e.g., a complex of TCRa and TCRP, a complex of TCRy and TCR8, a complex of CD3e and CD38, a complex of CD3y and CD3e, or a sub-TCR complex of TCRa, TCRp, CD3y, CD38, and two CD3s chains). 2023204645   13 Jul 2023 The term "chimeric antigen receptor" or "CAR" refers to a fusion protein that is engineered to contain two or more amino acid sequences linked together in a way that does not occur naturally or does not occur naturally in a host cell, which fusion protein can function as a receptor when present on a surface of a cell. CARs encompassed by the 5 present invention include an extracellular portion comprising an antigen-binding domain (i.e., obtained or derived from an immunoglobulin or immunoglobulin-like molecule, such as a TCR specific for an HA-2 antigen, a single chain TCR-derived binding protein, an scFv derived from an antibody, an antigen binding domain derived or obtained from a killer immunoreceptor from an NK cell, and the like) linked to a transmembrane domain and one 10 or more intracellular signaling domains (such as an effector domain, optionally containing co-stimulatory domain(s)) (see, e.g., Sadelain et al. (2013) Cancer Discov. 3:388; see also Harris and Kranz (2016) Trends Pharmacol. Sci. 37: 220; Stone et al. (2014) Cancer Immunol. Immunother. 63:1163). As used herein, the term “cytotoxic T lymphocyte (CTL) response” refers to an 15 immune response induced by cytotoxic T cells. CTL responses are mediated primarily by CD8+ T cells. The term "consisting essentially of is not equivalent to "comprising" and refers to the specified materials or steps of a claim, or to those that do not materially affect the basic characteristics of a claimed subject matter. For example, a protein domain, region, or 20 module (e.g., a binding domain, hinge region, linker module) or a protein (which may have one or more domains, regions, or modules) "consists essentially of a particular amino acid sequence when the amino acid sequence of a domain, region, module, or protein includes extensions, deletions, mutations, or a combination thereof (e.g., amino acids at the amino-or carboxy -terminus or between domains) that, in combination, contribute to at most 20% 25   (e.g., at most 15%, 10%, 8%, 6%, 5%, 4%, 3%, 2% or 1%) of the length of a domain, region, module, or protein and do not substantially affect (i.e., do not reduce the activity by more than 50%, such as no more than 40%, 30%, 25%, 20%, 15%, 10%, 5%, or 1%) the activity of the domain(s), region(s), module(s), or protein (e.g., the target binding affinity of a binding protein). 30          The term “determining a suitable treatment regimen for the subject” is taken to mean the determination of a treatment regimen (i.e., a single therapy or a combination of different therapies that are used for the prevention and / or treatment of the viral infection in the subject) for a subject that is started, modified and / or ended based or essentially based or 2023204645   13 Jul 2023 at least partially based on the results of the analysis according to the present invention. One example is starting an adjuvant therapy after surgery whose purpose is to decrease the risk of recurrence, another would be to modify the dosage of a particular chemotherapy. The determination can, in addition to the results of the analysis according to the present 5 invention, be based on personal characteristics of the subject to be treated. In most cases, the actual determination of the suitable treatment regimen for the subject will be performed by the attending physician or doctor. As used herein, a "hematopoietic progenitor cell" is a cell that can be derived from hematopoietic stem cells or fetal tissue and is capable of further differentiation into mature 10 cells types (e.g., immune system cells). Exemplary hematopoietic progenitor cells include those with a CD24Lo Lin- CD 117+ phenotype or those found in the thymus (referred to as progenitor thymocytes). “Homologous” as used herein, refers to nucleotide sequence similarity between two regions of the same nucleic acid strand or between regions of two different nucleic acid 15 strands. When a nucleotide residue position in both regions is occupied by the same nucleotide residue, then the regions are homologous at that position. A first region is homologous to a second region if at least one nucleotide residue position of each region is occupied by the same residue. Homology between two regions is expressed in terms of the proportion of nucleotide residue positions of the two regions that are occupied by the same 20 nucleotide residue. By way of example, a region having the nucleotide sequence 5'-ATTGCC-3' and a region having the nucleotide sequence 5'-TATGGC-3' share 50% homology. In some embodiments, the first region comprises a first portion and the second region comprises a second portion, whereby, at least about 50%, and, in other embodiments, at least about 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 25   86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more, or any range in between, inclusive, such as at least about 80%-100%, of the nucleotide residue positions of each of the portions are occupied by the same nucleotide residue. In some embodiments, all nucleotide residue positions of each of the portions are occupied by the same nucleotide residue. 30          As used herein, the term "HA-2 antigen" or "HA-2 peptide antigen" or "HA-2- containing peptide antigen" or “HA-2 epitope” or “HA-2 peptide epitope” or “HA-2 peptide” refers to a naturally or synthetically produced peptide portion of a member of the class I myosin family known as MY01G (Pierce et al. (2001) J. Immunol. 167:3223-3230). 2023204645   13 Jul 2023 The gene is located on the short arm of chromosome 7 in humans and its expression is limited to cells of hematopoietic origin. MY01G is a diallelic gene encoding two genetic variants, designated MYOIG(V) and MYOIG(M). MYOIG(V) encodes the YIGEVLVSV HA-2 epitope and MYOIG(M) encodes the YIGEVLVSM HA-2 epitope. The single 5 amino acid change between the two peptides has only a modest effects on peptide binding to the class I MHC-restricted element HLA-A (e.g., HLA-A*0201) and on recognition by T cells when added exogenously to target cells. However, the peptide encoded by MYOIG(M) is believed not to be presented at the surface of cells that endogenously express the MYOIG(M) allele. HA-2 antigen protein can range in length from about 7 10 amino acids, about 8 amino acids, about 9 amino acids, about 10 amino acids, up to about 20 amino acids, and can form a complex with a MHC (e.g., HLA) molecule such that a binding protein of this disclosure specific for an HA-2 peptide:MHC (e.g., HLA) complex can bind (e.g., specifically and / or selectively) to such as complex. An exemplary HA-2 peptide antigen comprises a peptide having the amino acid YIGEVLVSV or YIGEVLVSM. 15 In some embodiments, the YIGEVLVSV peptide sequence is referred to as “HA-2 REF” and the YIGEVLVSM peptide sequence is referred to as “HA-2 SNP”. The term "hyperproliferative disorder characterized by expression of an HA-2 antigen" can be any hyperproliferative disorder where the HA-2 antigen is present in a MHC (e.g., HLA) complex expressed by at least some hyperproliferating cells in the 20 subject. Examples of hyperproliferative disorders characterized by HA-2:HLA complexes include hematological malignancies. In certain embodiments, the hematological malignancy comprises a leukemia (e.g., an acute leukemia or a chronic leukemia). In specific embodiments, the leukemia comprises acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), mixed phenotype acute leukemia (MPAL), chronic myeloid 25 leukemia (CML), B cell prolymphocytic leukemia, hairy cell leukemia, or chronic lymphocytic leukemia (CLL). In certain embodiments, the hematological malignancy comprises a lymphoma. In certain embodiments, the lymphoma comprises Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), a central nervous system lymphoma, small lymphocytic lymphoma (SLL), CD37+ dendritic cell lymphoma, lymphoplasmacytic 30 lymphoma, splenic marginal zone lymphoma, plasma cell myeloma, extraosseous plasmacytoma, extra-nodal marginal zone B-cell lymphoma of mucosa-associated (MALT) lymphoid tissue, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, mediastinal (thymic) large B-cell lymphoma, 2023204645   13 Jul 2023 precursor B-lymphoblastic lymphoma, immunoblastic large cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma / leukemia, B-cell proliferations of uncertain malignant potential, lymphomatoid granulomatosis, and posttransplant lymphoproliferative disorder. In certain embodiments, the hematological 5 malignancy comprises a myelodysplastic disorder (MDS), such as, for example, refractory cytopenia with unilineage dysplasia (refractory anemia, refractory neutropenia, and refractory thrombocytopenia), refractory anemia with ring sideroblasts (RARS), refractory anemia with ring sideroblasts - thrombocytosis (RARS-t), refractory cytopenia with multinieage dysplasia (RCMD), refractory cytopenia with multinieage dysplasia and ring 10 sideroblasts (RCMD-RS), refractory anemia with excess blasts (RAEB), myelodysplasia unclassifiable, refractory cytopenia of childhood, MDS with isolated del(5q), and other well-known MDS subtypes (see, for example, 2016 World Health Organization MDS classification available on the World Wide Web at nbci.nlm.nih.gov / pmc / articles / PMC655460 / ). In certain embodiments, the hematological 15 malignancy comprises a myeloproliferative neoplasms (MPN), such as for example, myelofibrosis, polycythemia vera, essential thrombocythemia, chronic myelomonocytic leukemia, chronic myeloproliferative disease-unclassifiable, chronic neutrophilic leukemia, chronic eosinophilic leukemia and MPN-not otherwise specified. In further embodiments, the hematological malignancy comprises a myeloma. 20          The term “immune response” includes T cell mediated and / or B cell mediated immune responses. Exemplary immune responses include T cell responses, e.g., cytokine production and cellular cytotoxicity. In addition, the term immune response includes immune responses that are indirectly effected by T cell activation, e.g., antibody production (humoral responses) and activation of cytokine responsive cells, e.g., macrophages. 25          An increased ability to stimulate an immune response or the immune system, can result from an enhanced agonist activity of T cell costimulatory receptors and / or an enhanced antagonist activity of inhibitory receptors. An increased ability to stimulate an immune response or the immune system may be reflected by a fold increase of the EC 50 or maximal level of activity in an assay that measures an immune response, e.g., an assay that 30 measures changes in cytokine or chemokine release, cytolytic activity (determined directly on target cells or indirectly via detecting CD 107a or granzymes) and proliferation. The ability to stimulate an immune response or the immune system activity may be enhanced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 110%, 120%, 130%, 2023204645   13 Jul 2023 140%, 150%, 160%, 170%, 180%, 190%, 200%, 250%, 300%, 350%, 400%, 500%, or more. The term “immunotherapeutic agent” may include any molecule, peptide, antibody or other agent which can stimulate a host immune system to generate an immune response 5 to a viral infection in the subject. Various immunotherapeutic agents are useful in the compositions and methods described herein. The term “immune cell” refers to any cell of the immune system that originates from a hematopoietic stem cell in the bone marrow, which gives rise to two major lineages: a myeloid progenitor cell (which give rise to myeloid cells such as monocytes, 10 macrophages, dendritic cells, megakaryocytes and granulocytes); and a lymphoid progenitor cell (which give rise to lymphoid cells such as T cells, B cells and natural killer (NK) cells). Exemplary immune system cells include a CD4+ T cell, a CD8+ T cell, a CD4 CD 8 double negative T cell, a gd T cell, a regulatory T cell, a natural killer cell, and a dendritic cell. Macrophages and dendritic cells may be referred to as “antigen presenting 15 cells” or “APCs,” which are specialized cells that can activate T cells when a major histocompatibility complex (MHC) receptor on the surface of the APC complexed with a peptide interacts with a TCR on the surface of a T cell. An “isolated protein” refers to a protein that is substantially free of other proteins, cellular material, separation medium, and culture medium when isolated from cells or 20 produced by recombinant DNA techniques, or chemical precursors or other chemicals when chemically synthesized. An “isolated” or “purified” protein or biologically active portion thereof is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the binding protein, antibody, polypeptide, peptide or fusion protein is derived, or substantially free from chemical precursors or other chemicals 25 when chemically synthesized. The language “substantially free of cellular material” includes preparations of a biomarker polypeptide or fragment thereof, in which the protein is separated from cellular components of the cells from which it is isolated or recombinantly produced. In one embodiment, the language “substantially free of cellular material” includes preparations of a biomarker protein or fragment thereof, having less than 30 about 30% (by dry weight) of non-biomarker protein (also referred to herein as a “contaminating protein”), or, in some embodiments, less than about 25%, 20%, 15%, 10%, 5%, 1%, or less, or any range in between inclusive, such as less than about 1% to 5%, of non-biomarker protein. When binding protein, antibody, polypeptide, peptide or fusion 2023204645   13 Jul 2023 protein or fragment thereof, e.g., a biologically active fragment thereof, is recombinantly produced, it may be substantially free of culture medium, i.e., culture medium represents less than about 20%, 15%, 10%, 5%, 1%, or less, or any range in between inclusive, such as less than about 1% to 5%, of the volume of the protein preparation. 5           As used herein, the term “isotype” refers to the antibody class (e.g., IgM, IgGl, IgG2C, and the like) that is encoded by heavy chain constant region genes. As used herein, the term “Kd” is intended to refer to the dissociation equilibrium constant of a particular binding protein-antigen interaction. The binding affinity of binding proteins encompassed by the present invention may be measured or determined by standard 10 binding protein-target binding assays, for example, competitive assays, saturation assays, or standard immunoassays, such as ELISA or RIA. A relatively lower Kd value indicates a relatively higher binding affinity (e.g., Kd values of less than or equal to about 5x10-4 M (500 uM) include a Kd value of IxlO-4 M (100 uM) and a 100 uM Kd indicates a relatively higher binding affinity as compared to a 500 uM Kd). 15          A “kit” is any manufacture (e.g., a package or container) comprising at least one reagent, e.g., a probe or small molecule, for specifically detecting and / or affecting the expression of a marker encompassed by the present invention. The kit may be promoted, distributed, or sold as a unit for performing the methods encompassed by the present invention. The kit may comprise one or more reagents necessary to express a composition 20 useful in the methods encompassed by the present invention. In some embodiments, the kit may further comprise a reference standard, e.g., a nucleic acid encoding a protein that does not affect or regulate signaling pathways controlling cell growth, division, migration, survival or apoptosis. One skilled in the art can envision many such control proteins, including, but not limited to, common molecular tags (e.g., green fluorescent protein and 25 beta-galactosidase), proteins not classified in any of pathway encompassing cell growth, division, migration, survival or apoptosis by GeneOntology reference, or ubiquitous housekeeping proteins. Reagents in the kit may be provided in individual containers or as mixtures of two or more reagents in a single container. In addition, instructional materials which describe the use of the compositions within the kit may be included. 30          As used herein, the term “linked” refers to the association of two or more molecules. The linkage may be covalent or non-covalent. The linkage also may be genetic (i.e., recombinantly fused). Such linkages may be achieved using a wide variety of art recognized techniques, such as chemical conjugation and recombinant protein production. 2023204645   13 Jul 2023 A "linker," in some embodiments, may refer to an amino acid sequence that connects two proteins, polypeptides, peptides, domains, regions, or motifs and may provide a spacer function compatible with interaction of the two sub-binding domains so that the resulting polypeptide retains a specific binding affinity (e.g., scTCR) to a target molecule or 5 retains signaling activity (e.g., TCR complex). In some embodiments, a linker is comprised of about two to about 35 amino acids, for instance, or about four to about 20 amino acids or about eight to about 15 amino acids or about 15 to about 25 amino acids. "Major histocompatibility complex" (MHC) refers to glycoproteins that deliver peptide antigens to a cell surface. MHC class I molecules are heterodimers having a 10 membrane spanning a chain (with three a domains) and a non-covalently associated b2 microglobulin. MHC class II molecules are composed of two transmembrane glycoproteins, a and b, both of which span the membrane. Each chain has two domains. MHC class I molecules deliver peptides originating in the cytosol to the cell surface, where a peptide antigen-MHC (pMHC) complex is recognized by CD8+ T cells. MHC class II 15 molecules deliver peptides originating in the vesicular system to the cell surface, where they are recognized by CD4+ T cells. Human MHC is referred to as human leukocyte antigen (HLA). The terms “prevent,” “preventing,” “prevention,” “prophylactic treatment,” and the like refer to reducing the probability of developing a disease, disorder, or condition in a 20 subject, who does not have, but is at risk of or susceptible to developing a disease, disorder, or condition. The term “prognosis” includes a prediction of the probable course and outcome of a viral infection or the likelihood of recovery from the disease. In some embodiments, the use of statistical algorithms provides a prognosis of a viral infection in an individual. For 25 example, the prognosis may be surgery, development of a clinical subtype of a viral infection, development of one or more clinical factors, or recovery from the disease. As used herein, “percent identity” between amino acid sequences is synonymous with “percent homology,” which can be determined using the algorithm of Karlin and Altschul (1990) Proc. Natl. Acad. Sci. USA 87:2264-2268, modified by Karlin and Altschul 30   (1993) Proc. Natl. Acad. Sci. USA 90:5873-5877. The noted algorithm is incorporated into the NBLAST and XBLAST programs of Altschul et al. (1990) J. Mol. Biol. 215:403-410. BLAST nucleotide searches are performed with the NBLAST program, score=100, wordlength=12, to obtain nucleotide sequences homologous to a polynucleotide described 2023204645   13 Jul 2023 herein. BLAST protein searches are performed with the XBLAST program, score=50, wordlength=3, to obtain amino acid sequences homologous to a reference polypeptide. To obtain gapped alignments for comparison purposes, Gapped BLAST is utilized as described in Altschul et al. (1997) Nuc. Acids Res. 25:3389-3402. When utilizing BLAST and 5 Gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST andNBLAST) maybe used. The phrase “pharmaceutically-acceptable carrier” means a pharmaceutically-acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, or solvent encapsulating material, involved in carrying or transporting the subject 10 compound from one organ, or portion of the body, to another organ, or portion of the body. The term “recombinant host cell” (or simply “host cell”) refers to a cell that comprises a nucleic acid that is not naturally present in the cell, such as a cell into which a recombinant expression vector has been introduced. It should be understood that cells according to the present invention is intended to refer not only to the particular subject cell, 15 but also encompasses progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term cell according to the present invention. The term “cancer response,” “response to immunotherapy,” or “response to 20 modulators of T-cell mediated cytotoxicity / immunotherapy combination therapy” relates to any response of the hyperproliferative disorder (e.g., cancer) to a cancer agent, such as a modulator of T-cell mediated cytotoxicity, and an immunotherapy, preferably to a change in tumor mass and / or volume after initiation of neoadjuvant or adjuvant therapy. The term “neoadjuvant therapy” refers to a treatment given before the primary treatment. Examples 25 of neoadjuvant therapy may include chemotherapy, radiation therapy, and hormone therapy. Hyperproliferative disorder response may be assessed, for example for efficacy or in a neoadjuvant or adjuvant situation, where the size of a tumor after systemic intervention may be compared to the initial size and dimensions as measured by CT, PET, mammogram, ultrasound or palpation. Responses may also be assessed by caliper measurement or 30 pathological examination of the tumor after biopsy or surgical resection. Response may be recorded in a quantitative fashion like percentage change in tumor volume or in a qualitative fashion like “pathological complete response” (pCR), “clinical complete remission” (cCR), “clinical partial remission” (cPR), “clinical stable disease” (cSD), 2023204645   13 Jul 2023 “clinical progressive disease” (cPD) or other qualitative criteria. Assessment of hyperproliferative disorder response may be done early after the onset of neoadjuvant or adjuvant therapy, e.g., after a few hours, days, weeks or preferably after a few months. A typical endpoint for response assessment is upon termination of neoadjuvant chemotherapy 5 or upon surgical removal of residual tumor cells and / or the tumor bed. This is typically three months after initiation of neoadjuvant therapy. In some embodiments, clinical efficacy of the therapeutic treatments described herein may be determined by measuring the clinical benefit rate (CBR). The clinical benefit rate is measured by determining the sum of the percentage of patients who are in complete remission (CR), the number of patients who 10 are in partial remission (PR) and the number of patients having stable disease (SD) at a time point at least 6 months out from the end of therapy. The shorthand for this formula is CBR=CR+PR+SD over 6 months. In some embodiments, the CBR for a particular cancer therapeutic regimen is at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or more. Additional criteria for evaluating the response to cancer 15 therapies are related to “survival,” which includes all of the following: survival until mortality, also known as overall survival (wherein said mortality may be either irrespective of cause or tumor related); “recurrence-free survival” (wherein the term recurrence shall include both localized and distant recurrence); metastasis free survival; disease free survival (wherein the term disease shall include cancer and diseases associated therewith). The 20 length of said survival may be calculated by reference to a defined start point (e.g., time of diagnosis or start of treatment) and end point (e.g., death, recurrence or metastasis). In addition, criteria for efficacy of treatment may be expanded to include response to chemotherapy, probability of survival, probability of metastasis within a given time period, and probability of tumor recurrence. For example, in order to determine appropriate 25 threshold values, a particular cancer therapeutic regimen may be administered to a population of subjects and the outcome may be correlated to biomarker measurements that were determined prior to administration of any cancer therapy. The outcome measurement may be pathologic response to therapy given in the neoadjuvant setting. Alternatively, outcome measures, such as overall survival and disease-free survival may be monitored 30 over a period of time for subjects following cancer therapy for which biomarker measurement values are known. In certain embodiments, the doses administered are standard doses known in the art for cancer therapeutic agents. The period of time for which subjects are monitored may vary. For example, subjects may be monitored for at least 2, 4, 2023204645   13 Jul 2023 6, 8, 10, 12, 14, 16, 18, 20, 25, 30, 35, 40, 45, 50, 55, or 60 months. Biomarker measurement threshold values that correlate to outcome of a cancer therapy may be determined using well-known methods in the art, such as those described in the Examples section. 5          As indicated, the terms may also refer to an improved prognosis, for example, as reflected by an increased time to recurrence, which is the period to first recurrence censoring for second primary cancer as a first event or death without evidence of recurrence, or an increased overall survival, which is the period from treatment to death from any cause. To respond or to have a response means there is a beneficial endpoint 10 attained when exposed to a stimulus. Alternatively, a negative or detrimental symptom is minimized, mitigated or attenuated on exposure to a stimulus. It will be appreciated that evaluating the likelihood that a tumor or subject will exhibit a favorable response is equivalent to evaluating the likelihood that the tumor or subject will not exhibit favorable response (i.e., will exhibit a lack of response or be non-responsive). 15           The term “resistance” refers to an acquired or natural resistance of a cancer sample or a mammal to a cancer therapy (i.e., being nonresponsive to or having reduced or limited response to the therapeutic treatment), such as having a reduced response to a therapeutic treatment by 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, or more, such 2-fold, 3-fold, 4-fold, 5-fold, 10 20 fold, 15-fold, 20-fold or more, or any range in between, inclusive. The reduction in response may be measured by comparing with the same cancer sample or mammal before the resistance is acquired, or by comparing with a different cancer sample or a mammal that is known to have no resistance to the therapeutic treatment. A typical acquired resistance to chemotherapy is called “multidrug resistance.” The multidrug resistance may be mediated 25 by P-glycoprotein or may be mediated by other mechanisms, or it may occur when a mammal is infected with a multi-drug-resistant microorganism or a combination of microorganisms. The determination of resistance to a therapeutic treatment is routine in the art and within the skill of an ordinarily skilled clinician, for example, may be measured by cell proliferative assays and cell death assays as described herein as “sensitizing.” In some 30 embodiments, the term “reverses resistance” means that the use of a second agent in combination with a primary cancer therapy (e.g., chemotherapeutic or radiation therapy) is able to produce a significant decrease in tumor volume at a level of statistical significance (e.g., p<0.05) when compared to tumor volume of untreated tumor in the circumstance 2023204645   13 Jul 2023 where the primary cancer therapy (e.g., chemotherapeutic or radiation therapy) alone is unable to produce a statistically significant decrease in tumor volume compared to tumor volume of untreated tumor. This generally applies to tumor volume measurements made at a time when the untreated tumor is growing logarithmically. 5          The term “sample” used for detecting or determining the absence, presence, or level of at least one biomarker is typically brain tissue, cerebrospinal fluid, whole blood, plasma, serum, saliva, urine, stool (e.g., feces), tears, and any other bodily fluid (e.g., as described above under the definition of “body fluids”), or a tissue sample (e.g., biopsy) such as a small intestine, colon sample, or surgical resection tissue. In some embodiments, methods 10 encompassed by the present invention further comprises obtaining the sample from the individual prior to detecting or determining the absence, presence, or level of at least one marker in the sample. The term “sensitize” means to alter cancer cells or tumor cells in a way that allows for more effective treatment of the associated cancer with a cancer therapy (e.g., anti- 15 immune checkpoint, chemotherapeutic, and / or radiation therapy). In some embodiments, normal cells are not affected to an extent that causes the normal cells to be unduly injured by the therapies. An increased sensitivity or a reduced sensitivity to a therapeutic treatment is measured according to a known method in the art for the particular treatment and methods described herein below, including, but not limited to, cell proliferative assays 20 (Tanigawa et al. (1982) Cancer Res. 42:2159-2164) and cell death assays (Weisenthal et al. (1984) Cancer Res. 94:161-173; Weisenthal et al. (1985) Cancer Treat Rep. 69:615-632; Weisenthal et al., In: Kaspers G J L, Pieters R, Twentyman P R, Weisenthal L M, Veerman A J P, eds. Drug Resistance in Leukemia and Lymphoma. Langhome, P A: Harwood Academic Publishers, 1993:415-432; Weisenthal (1994) Contrib. Gynecol. Obstet. 19:82 25   90). The sensitivity or resistance may also be measured in animal by measuring the tumor size reduction over a period of time, for example, 6 month for human and 4-6 weeks for mouse. A composition or a method sensitizes response to a therapeutic treatment if the increase in treatment sensitivity or the reduction in resistance is 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, or 30 more, such 2-fold, 3-fold, 4-fold, 5-fold, 10-fold, 15-fold, 20-fold or more, or any range in between, inclusive, compared to treatment sensitivity or resistance in the absence of such composition or method. The determination of sensitivity or resistance to a therapeutic treatment is routine in the art and within the skill of an ordinarily skilled clinician. It is to 2023204645   13 Jul 2023 be understood that any method described herein for enhancing the efficacy of a cancer therapy may be equally applied to methods for sensitizing hyperproliferative or otherwise cancerous cells (e.g., resistant cells) to the cancer therapy. The term “small molecule” is a term of the art and includes molecules that are less 5 than about 1000 molecular weight or less than about 500 molecular weight. In one embodiment, small molecules do not exclusively comprise peptide bonds. In another embodiment, small molecules are not oligomeric. Exemplary small molecule compounds which may be screened for activity include, but are not limited to, peptides, peptidomimetics, nucleic acids, carbohydrates, small organic molecules (e.g., polyketides) 10 (Cane et al. (1998) Science 282:63-68), and natural product extract libraries. In another embodiment, the compounds are small, organic non-peptidic compounds. In a further embodiment, a small molecule is not biosynthetic. The term “specific binding” refers to binding protein binding to a predetermined antigen. Typically, the binding protein binds with an affinity (Kd) of approximately less 15 than or equal to about 5xl0-4 M, less than or equal to about IxlO-4 M, less than or equal to about 5xl0-5 M, less than or equal to about IxlO-5 M, less than or equal to about 5x1 O’6 M, less than or equal to about IxlO-6 M, less than or equal to about 5xl0-7 M, less than or equal to about IxlO-7 M, less than or equal to about 5xl0-8 M, less than or equal to about IxlO-8 M, less than or equal to about 5xl0-9 M, less than or equal to about IxlO-9 M, less than or 20 equal to about 5xlO-10 M, less than or equal to about IxlO-10 M, less than or equal to about 5xl0-11 M, less than or equal to about IxlO-11 M, less than or equal to about 5xl0-12 M, less than or equal to about IxlO-12 M, or even lower, or any range in between, inclusive, such as between about 1-50 micromolar, 1-100 micromolar, 0.1-500 micromolar, and the like,when determined by a binding assay, such as surface plasmon resonance (SPR) technology in a 25 BIAcore™ assay instrument using an antigen of interest as the analyte and the binding protein as the ligand. In some embodiments, the binding protein binds to the predetermined antigen with an affinity that is at least 1.1-, 1.2-, 1.3-, 1.4-, 1.5-, 1.6-, 1.7-, 1.8-, 1.9-,2.0-, 2.5-, 3.0-, 3.5-, 4.0-, 4.5-, 5.0-, 6.0-, 7.0-, 8.0-, 9.0-, or 10.0-fold or greater than its affinity for binding to a non-specific antigen (e.g., BSA, casein) other than the predetermined 30 antigen or a closely-related antigen. The phrases “a binding protein recognizing an antigen” and “a binding protein specific for an antigen” are used interchangeably herein with the term “a binding protein which binds specifically to an antigen.” Selective binding is a relative term referring to the ability of a binding protein to discriminate the binding of 2023204645   13 Jul 2023 one antigen over another, such as a particular family member or antigen target over a related family member or antigen target. For example, analytical data provided in the Examples section demonstrate that binding proteins described herein specifically bind HA-2 immunogenic epitopes and / or selectively bind a number of related epitopes (e.g., HA-2 5 immunogenic epitopes and closely related sequences) discriminating such targets from the vast majority of other possible epitopes available in the human genome. The term “subject” refers to any healthy animal, mammal or human, or any animal, mammal or human afflicted with a non-malignant disorder, a hyperproliferative disorder, or a relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen. 10 The term “subject” is interchangeable with “patient.” The term “survival” includes all of the following: survival until mortality, also known as overall survival (wherein said mortality may be either irrespective of cause or tumor related); “recurrence-free survival” (wherein the term recurrence shall include both localized and distant recurrence); metastasis free survival; disease free survival (wherein 15 the term disease shall include cancer and diseases associated therewith). The length of said survival may be calculated by reference to a defined start point (e.g., time of diagnosis or start of treatment) and end point (e.g., death, recurrence or metastasis). In addition, criteria for efficacy of treatment may be expanded to include response to chemotherapy, probability of survival, probability of metastasis within a given time period, and probability of tumor 20 recurrence. The term “synergistic effect” refers to the combined effect of two or more agents (e.g., an HA-2-related agent described herein and another therapy for treating a disorder characterized by HA-2 expression) that is greater than the sum of the separate effects of the cancer agents / therapies alone. 25          As used herein, the term “T cell-mediated response” refers to a response mediated by T cells, including effector T cells (e.g., CD8+ cells) and helper T cells (e.g., CD4+ cells). T cell mediated responses include, for example, T cell cytotoxicity and proliferation. A “transcribed polynucleotide” or “nucleotide transcript” is a polynucleotide (e.g., an mRNA, hnRNA, a cDNA, or an analog of such RNA or cDNA) which is complementary 30 to or homologous with all or a portion of a mature mRNA made by transcription of a biomarker nucleic acid and normal post-transcriptional processing (e.g., splicing), if any, of the RNA transcript, and reverse transcription of the RNA transcript. 2023204645   13 Jul 2023 A “T cell” is an immune system cell that matures in the thymus and produces T cell receptors (TCRs). T cells may be naive (not exposed to antigen; increased expression of CD62L, CCR7, CD28, CD3, CD 127, and CD45RA, and decreased expression of CD45RO as compared to Tcm), memory T cells (Tm) (antigen-experienced and long-lived), and 5 effector cells (antigen-experienced, cytotoxic). Tm may be further divided into subsets of central memory T cells (Tcm, increased expression of CD62L, CCR7, CD28, CD 127, CD45RO, and CD95, and decreased expression of CD54RA as compared to naive T cells) and effector memory T cells (Tem, decreased expression of CD62L, CCR7, CD28, CD45RA, and increased expression of CD 127 as compared to naive T cells or Tcm). 10 Effector T cells (Te) refers to antigen-experienced CD8+ cytotoxic T lymphocytes that have decreased expression of CD62L ,CCR7, CD28, and are positive for granzyme and perforin as compared to Tcm. Other exemplary T cells include regulatory T cells, such as CD4+ CD25+ (Foxp3+) regulatory T cells and Tregl7 cells, as well as Tri, Th3, CD8+CD28, and Qa-1 restricted T cells. 15           Conventional T cells, also known as Tconv or Teffs, have effector functions (e.g., cytokine secretion, cytotoxic activity, anti-self-recognition, and the like) to increase immune responses by virtue of their expression of one or more T cell receptors. Tcons or Teffs are generally defined as any T cell population that is not a Treg and include, for example, naive T cells, activated T cells, memory T cells, resting Tcons, or Tcons that have 20 differentiated toward, for example, the Thl or Th2 lineages. In some embodiments, Teffs are a subset of non-Treg T cells. In some embodiments, Teffs are CD4+ Teffs or CD8+ Teffs, such as CD4+ helper T lymphocytes (e.g., ThO, Thl, Tfh, or Thl7) and CD8+ cytotoxic T lymphocytes. As described further herein, cytotoxic T cells are CD 8+ T lymphocytes. “Naive Tcons” are CD4+ T cells that have differentiated in bone marrow, and 25 successfully underwent a positive and negative processes of central selection in a thymus, but have not yet been activated by exposure to an antigen. Naive Tcons are commonly characterized by surface expression of L-selectin (CD62L), absence of activation markers such as CD25, CD44 or CD69, and absence of memory markers such as CD45RO. Naive Tcons are therefore believed to be quiescent and non-dividing, requiring interleukin-7 (IL- 30   7) and interleukin-15 (IL- 15) for homeostatic survival (see, at least WO 2010 / 101870). The presence and activity of such cells are undesired in the context of suppressing immune responses. Unlike Tregs, Tcons are not anergic and can proliferate in response to antigen- 2023204645   13 Jul 2023 based T cell receptor activation (Lechler et al. (2001) Philos. Trans. R. Soc. Land. Biol. Sci. 356:625-637). “T effector” (“Teff” or “Te”) cells refers to T cells (e.g., CD4+ and CD8+ T cells) with cytolytic activities as well as T helper (Th) cells, which secrete cytokines and activate 5 and direct other immune cells, but does not include regulatory T cells (Treg cells). "T cell receptor" or "TCR" refers to an immunoglobulin superfamily member (having a variable binding domain, a constant domain, a transmembrane region, and a short cytoplasmic tail; see, e.g., Janeway et al. (1997) Curr. Biol. Publ. 4:33) that is capable of binding (e.g., specifically and / or selectively) to an antigen peptide bound to a MHC 10 receptor. A TCR can be found on the surface of a cell or in soluble form and generally is comprised of a heterodimer having alpha and beta chains (also known as TCRa and TCRp, respectively), or y and 8 chains (also known as TCRy and TCR8, respectively). Like immunoglobulins (e.g., antibodies), the extracellular portion of TCR chains (e.g., a-chain and P-chain) contain two immunoglobulin domains: a variable domain (e.g., a-chain 15 variable domain or Na and P-chain variable domain or Vp; typically amino acids 1 to 116 based on Kabat numbering (Kabat et al. (1991) "Sequences of Proteins of Immunological Interest, US Dept. Health and Human Services, Public Health Service National Institutes of Health, 5th ed.) at the N-terminal end, and one constant domain (e.g., a-chain constant domain or Ca, typically amino acids 117 to 259 based on Kabat, P-chain constant domain or 20 Cp, typically amino acids 117 to 295 based on Kabat) at the C-terminal end and adjacent to the cell membrane. Also like immunoglobulins, the variable domains contain complementary determining regions (“CDRs”, also called hypervariable regions or “HVRs”) separated by framework regions (“FRs”) (see, e.g., Fores et al. (1990) Proc. Natl. Acad Sci. US.A. 87:9138; Chothia et al. (1988) EMBO J. 7:3745; Lefranc et al. (2003) Dev. 25 Comp. Immunol. 27:55). In some embodiments, a TCR is found on the surface of a T cell (or T lymphocyte) and associates with the CD3 complex. The source of a TCR encompassed by the present invention may be from various animal species, such as a human, mouse, rat, rabbit or other mammal. The term “T cell receptor” or “TCR” should be understood to encompass full TCRs 30 as well as antigen-binding portions or antigen-binding fragments thereof. In some embodiments, the TCR is an intact or full-length TCR, including TCRs in the aP form or y8 form. In some embodiments, the TCR is an antigen-binding portion that is less than a fulllength TCR but that binds to a specific peptide bound in an MHC molecule, such as binds 2023204645   13 Jul 2023 to an MHC-peptide complex. In some cases, an antigen-binding portion or fragment of a TCR may contain only a portion of the structural domains of a full-length or intact TCR, but yet is able to bind the peptide epitope, such as MHC-peptide complex, to which the full TCR binds. In some cases, an antigen-binding portion contains the variable domains of a 5 TCR, such as variable a chain and variable p chain of a TCR, sufficient to form a binding site for binding to a specific MHC-peptide complex. Generally, the variable chains of a TCR contain complementarity determining regions (CDRs) involved in recognition of the peptide, MHC and / or MHC-peptide complex. Nomenclature established by the International Immunogenetics Information System 10 (IMGT) (see also Scaviner and Lefranc (2000) Exp. Clin. Immunogenet. 17:83-96 and 97106; Folch and Lefranc (2000) Exp. Clin. Immunogenet, 17:107-114; T Cell Receptor Factsbook", (2001) LeFranc and LeFranc, Academic Press, ISBN 0-12-441352-8). The IMGT provides unique sequences used to describe a TCR, and sequences described herein may be identified by reference to such unique sequences provided herein. TCR sequences 15 are publicly available at the IMGT database at imgt.org. As described above, native alpha / beta heterodimeric TCRs have an alpha chain and a beta chain. Broadly, each chain comprises variable, joining and constant regions, and the beta chain also usually contains a short diversity region between the variable and joining regions, but this diversity region is often considered as part of the joining region. Each 20 variable region comprises three hypervariable CDRs (Complementarity Determining Regions) embedded in a framework sequence. CDR3 is well-known to be the main mediator of antigen recognition. There are several types of alpha chain variable (Va) regions and several types of beta chain variable (Vp) regions distinguished by their framework, CDR1 and CDR2 sequences, and by a partly defined CDR3 sequence. The Va 25 types are referred to in IMGT nomenclature by a unique TRAV number. For example, "TRAV4" defines a TCR Va region having unique framework and CDR1 and CDR2 sequences, and a CDR3 sequence which is partly defined by an amino acid sequence which is preserved from TCR to TCR but which also includes an amino acid sequence which varies from TCR to TCR. Similarly, "TRBV2" defines a TCR VP region having unique 30 framework and CDR1 and CDR2 sequences, but with only a partly defined CDR3 sequence. It is known that there are 54 alpha variable genes, of which 44 are functional, and 67 beta variable genes, of which 42 are functional, within the alpha and beta loci, respectively. 2023204645   13 Jul 2023 The joining regions of the TCR are similarly defined by the unique IMGT TRAJ and TRBJ nomenclature, and the constant regions by the IMGT TRAC and TRBC nomenclature. The beta chain diversity region is referred to in IMGT nomenclature by the abbreviation TRBD, and, as mentioned, the concatenated TRBD / TRBJ regions are often 5 considered together as the joining region. The gene pools that encode the TCR alpha and beta chains are located on different chromosomes and contain separate V, (D), J and C gene segments, which are brought together by rearrangement during T cell development. This leads to a very high diversity of T cell alpha and beta chains due to the large number of potential recombination events that 10 occur between the 54 TCR alpha variable genes and 61 alpha J genes or between the 67 beta variable genes, two beta D genes and 13 beta J genes. The recombination process is not precise and introduces further diversity within the CDR3 region. Each alpha and beta variable gene may also comprise allelic variants, designated in IMGT nomenclature as TRAVxx*01 and *02, or TRBVx-x*01 and *02 respectively, thus further increasing the 15 amount of variation. In the same way, some of the TRBJ sequences have two known variations. (Note that the absence of a "*" qualifier means that only one allele is known for the relevant sequence). The natural repertoire of human TCRs resulting from recombination and thymic selection has been estimated to comprise approximately 106 unique beta chain sequences, determined from CDR3 diversity (Arstila et al. (1999) Science 20   286:958-961) and could be even higher (Robins et al. (2009) Blood 114:4099-4107). Each beta chain is estimated to pair with at least 25 different alpha chains, thus generating further diversity (Arstila et al. (1999) Science 286:958-961). The term "TCR alpha variable domain" therefore refers to the concatenation of TRAV and TRAJ regions; a TRAV region only; or TRAV and a partial TRAJ region, 25 and the term TCR alpha constant domain refers to the extracellular TRAC region, or to a C-terminal truncated or full length TRAC sequence. Likewise the term "TCR beta variable domain" refers to the concatenation of TRBV and TRBD / TRBJ regions; to the TRBV and TRBD regions only; to the TRBV and TRBJ regions only; or to the TRBV and partial TRBD and / or TRBJ regions, and the term TCR beta constant domain refers to the 30 extracellular TRBC region, or to a C-terminal truncated or full length TRBC sequence. These TCR alpha variable domain and TCR beta variable domain nomenclature similarly applies to the variable domains of TCR gamma and TCR delta chains, respectively, for 2023204645   13 Jul 2023 gamma / delta TCRs. An ordinarily skilled artisan can obtain TRAV, TRAJ, TRAC, TRBV, TRBJ, and TRBC gene sequences, such as through the publicly available IMGT database. The term "TCR complex" refers to a complex formed by the association of CD3 with TCR. For example, a TCR complex may be composed of a CD3y chain, a CD38 5 chain, two CD3s chains, a homodimer of CD3^ chains, a TCRa chain, and a TCRp chain. Alternatively, a TCR complex may be composed of a CD3y chain, a CD38 chain, two CD3s chains, a homodimer of CD3^ chains, a TCRy chain, and a TCRS chain. The term “therapeutic effect” refers to a local or systemic effect in animals, particularly mammals, and more particularly humans, caused by a pharmacologically active 10 substance. The term thus means any substance intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease or in the enhancement of desirable physical or mental development and conditions in an animal or human. The terms “therapeutically effective amount” and “effective amount” means that amount of a substance that produces some desired effect, such as a desired local or systemic 15 therapeutic effect, in at least a sub-population of cells in an animal at a reasonable benefit / risk ratio applicable to any treatment. In some embodiments, a therapeutically effective amount of a substance will depend on the substance's therapeutic index, solubility, pharmacokinetics, half-life, and the like. Toxicity and therapeutic efficacy of subject compounds may be determined by standard pharmaceutical procedures in cell cultures or 20 experimental animals, e.g., for determining the LD50 and the ED50. In some embodiments, compositions that exhibit large therapeutic indices are used. In some embodiments, the LD50 (lethal dosage) may be measured and may be, for example, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, 1000% or more reduced for the agent relative to no administration of the agent. 25 Similarly, the ED50 (i.e., the concentration which achieves a half-maximal inhibition of symptoms) may be measured and may be, for example, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, 1000% or more increased for the agent relative to no administration of the agent. Also, similarly, the IC50 may be measured and may be, for example, at least 10%, 20%, 30%, 30   40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, 1000% or more increased for the agent relative to no administration of the agent. In some embodiments, T cell immune response in an assay may be increased by at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 2023204645   13 Jul 2023 85%, 90%, 95%, or even 100%. In another embodiment, at least about a 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or even 100% decrease in a viral load may be achieved. The term “treat” refers to the therapeutic management or improvement of a 5 condition (e.g., a disease or disorder) of interest. Treatment may include, but is not limited to, administering an agent or composition (e.g., a pharmaceutical composition) to a subject. Treatment is typically undertaken in an effort to alter the course of a disease (which term is used to indicate any disease, disorder, syndrome or undesirable condition warranting or potentially warranting therapy) in a manner beneficial to the subject. The effect of 10 treatment may include reversing, alleviating, reducing severity of, delaying the onset of, curing, inhibiting the progression of, and / or reducing the likelihood of occurrence or recurrence of the disease or one or more symptoms or manifestations of the disease. Desirable effects of treatment include, but are not limited to, preventing occurrence or recurrence of disease, alleviation of symptoms, diminishment of any direct or indirect 15 pathological consequences of the disease, preventing metastasis, decreasing the rate of disease progression, amelioration or palliation of the disease state, and remission or improved prognosis. A therapeutic agent may be administered to a subject who has a disease or is at increased risk of developing a disease relative to a member of the general population. In some embodiments, a therapeutic agent may be administered to a subject 20 who has had a disease but no longer shows evidence of the disease. The agent may be administered e.g., to reduce the likelihood of recurrence of evident disease. A therapeutic agent may be administered prophylactically, i.e., before development of any symptom or manifestation of a disease. “Prophylactic treatment” refers to providing medical and / or surgical management to a subject who has not developed a disease or does not show 25 evidence of a disease in order, e.g., to reduce the likelihood that the disease will occur or to reduce the severity of the disease should it occur. The subject may have been identified as being at risk of developing the disease (e.g., at increased risk relative to the general population or as having a risk factor that increases the likelihood of developing the disease. The term “unresponsiveness” includes refractivity of cancer cells to therapy or 30 refractivity of therapeutic cells, such as immune cells, to stimulation, e.g., stimulation via an activating receptor or a cytokine. Unresponsiveness may occur, e.g., because of exposure to immunosuppressants or exposure to high doses of antigen. As used herein, the term “anergy” or “tolerance” includes refractivity to activating receptor-mediated 2023204645   13 Jul 2023 stimulation. Such refractivity is generally antigen-specific and persists after exposure to the tolerizing antigen has ceased. For example, anergy in T cells (as opposed to unresponsiveness) is characterized by lack of cytokine production, e.g., IL-2. T cell anergy occurs when T cells are exposed to antigen and receive a first signal (a T cell receptor or 5 CD-3 mediated signal) in the absence of a second signal (a costimulatory signal). Under these conditions, reexposure of the cells to the same antigen (even if reexposure occurs in the presence of a costimulatory polypeptide) results in failure to produce cytokines and, thus, failure to proliferate. Anergic T cells may, however, proliferate if cultured with cytokines (e.g., IL-2). For example, T cell anergy may also be observed by the lack of IL-2 10 production by T lymphocytes as measured by ELISA or by a proliferation assay using an indicator cell line. Alternatively, a reporter gene construct may be used. For example, anergic T cells fail to initiate IL-2 gene transcription induced by a heterologous promoter under the control of the 5’ IL-2 gene enhancer or by a multimer of the API sequence that may be found within the enhancer (Kang et al. (1992) Science 257:1134). 15          The term "variable region" or "variable domain" refers to the domain of an immunoglobulin superfamily binding protein (e.g., a TCR a-chain or P-chain (or y chain and 8 chain for y8 TCRs)) that is involved in binding of the immunoglobulin superfamily binding protein (e.g., TCR) to antigen. The variable domains of the a-chain and p-chain (Va and Vp, respectively) of a native TCR generally have similar structures, with each 20 domain comprising four conserved framework regions (FRs) and three CDRs. The Va domain is encoded by two separate DNA segments, the variable gene segment and the joining gene segment (V-J); the Vp domain is encoded by three separate DNA segments, the variable gene segment, the diversity gene segment, and the joining gene segment (V-D-J). A single Va or Vp domain may be sufficient to confer antigen-binding specificity. 25 Furthermore, TCRs that bind a particular antigen may be isolated using a Va or Vp domain from a TCR that binds the antigen to screen a library of complementary Va or Vp domains, respectively. The term “vector” refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. In some embodiments, a vector is an episome, i.e., 30 a nucleic acid capable of extra-chromosomal replication. In some embodiments, vectors are those capable of autonomous replication and / or expression of nucleic acids to which they are linked. Vectors capable of directing the expression of genes to which they are operatively linked are referred to herein as “expression vectors”. In general, expression 2023204645   13 Jul 2023 vectors of utility in recombinant DNA techniques are often in the form of “plasmids” which refer generally to circular double stranded DNA loops, which, in their vector form are not bound to the chromosome. In the present specification, “plasmid” and “vector” are used interchangeably as the plasmid is the most commonly used form of vector. However, as 5 will be appreciated by those skilled in the art, the present invention is intended to include such other forms of expression vectors that serve equivalent functions and which become subsequently known in the art. There is a known and definite correspondence between the amino acid sequence of a particular protein and the nucleotide sequences that can code for the protein, as defined by 10 the genetic code (shown below). Likewise, there is a known and definite correspondence between the nucleotide sequence of a particular nucleic acid and the amino acid sequence encoded by that nucleic acid, as defined by the genetic code. GENETIC CODE 15 Alanine (Ala, A) Arginine (Arg, R) Asparagine (Asn, N) Aspartic acid (Asp, D) Cysteine (Cys, C) GCA, GCC, GCG, GCT AGA, ACG, CGA, CGC, CGG, CGT AAC, AAT GAC, GAT TGC, TGT 20 Glutamic acid (Glu, E) Glutamine (Gin, Q) Glycine (Gly, G) Histidine (His, H) Isoleucine (He, I) GAA, GAG CAA, CAG GGA, GGC, GGG, GGT CAC, CAT ATA, ATC, ATT 25 Leucine (Leu, L) Lysine (Lys, K) Methionine (Met, M) Phenylalanine (Phe, F) Proline (Pro, P) CTA, CTC, CTG, CTT, TTA, TTG AAA, AAG ATG TTC, TTT CCA, CCC, CCG, CCT 30 Serine (Ser, S) Threonine (Thr, T) Tryptophan (Trp, W) Tyrosine (Tyr, Y) Valine (Vai, V) AGC, AGT, TCA, TCC, TCG, TCT ACA, ACC, ACG, ACT TGG TAC, TAT GTA, GTC, GTG, GTT 2023204645   13 Jul 2023 Termination signal (end)          TAA, TAG, TGA An important and well-known feature of the genetic code is its redundancy, whereby, for most of the amino acids used to make proteins, more than one coding 5 nucleotide triplet may be employed (illustrated above). Therefore, a number of different nucleotide sequences may code for a given amino acid sequence. Such nucleotide sequences are considered functionally equivalent since they result in the production of the same amino acid sequence in all organisms (although certain organisms may translate some sequences more efficiently than they do others). Moreover, occasionally, a methylated 10 variant of a purine or pyrimidine may be found in a given nucleotide sequence. Such methylations do not affect the coding relationship between the trinucleotide codon and the corresponding amino acid. In view of the foregoing, the nucleotide sequence of a DNA or RNA encoding a biomarker nucleic acid (or any portion thereof) may be used to derive the polypeptide 15   amino acid sequence, using the genetic code to translate the DNA or RNA into an amino acid sequence. Likewise, for polypeptide amino acid sequence, corresponding nucleotide sequences that can encode the polypeptide can be deduced from the genetic code (which, because of its redundancy, will produce multiple nucleic acid sequences for any given amino acid sequence). Thus, description and / or disclosure herein of a nucleotide sequence 20 which encodes a polypeptide should be considered to also include description and / or disclosure of the amino acid sequence encoded by the nucleotide sequence. Similarly, description and / or disclosure of a polypeptide amino acid sequence herein should be considered to also include description and / or disclosure of all possible nucleotide sequences that can encode the amino acid sequence. 25 IL Binding Proteins In an aspect encompassed by the present invention, provided herein are binding proteins that bind (e.g., specifically and / or selectively) to a peptide-MHC (pMHC) complex (e.g., MHC complex that stably presents a peptide) comprising an HA-2 immunogenic 30 peptide in the context of an MHC molecule (e.g., a MHC class I molecule). In some embodiments, the binding protein is capable of binding (e.g., specifically and / or selectively) to an HA-2 peptide-MHC (pMHC) complex with a Kd less than or equal to about 5xl0-4 M, less than or equal to about IxlO-4 M, less than or equal to about 5xl0-5 M, less than or equal to about IxlO-5 M, less than or equal to about 5x10-6 M, less than or equal 2023204645   13 Jul 2023 to about IxlO-6 M, less than or equal to about 5xl0-7 M, less than or equal to about IxlO-7 M, less than or equal to about 5xl0-8 M, less than or equal to about IxlO-8 M, less than or equal to about 5xl0-9 M, less than or equal to about IxlO-9 M, less than or equal to about 5xlO-10 M, less than or equal to about IxlO-10 M, less than or equal to about 5xl0-11 M, less 5 than or equal to about IxlO-11 M, less than or equal to about 5xl0-12 M, less than or equal to about IxlO-12 M, or any range in between, inclusive, such as between about 1-50 micromolar, 1-100 micromolar, 0.1-500 micromolar, and the like. In some embodiments, the MHC molecule comprises an MHC alpha chain that is an HLA serotype HLA-A*02. In some embodiments, the HLA allele is selected from the group consisting of HLA-A*0201, 10   HLA-A*0202, HLA-A*0203, HLA-A*0205, HLA-A*0206, and HLA-A*0207 allele. In a specific embodiment, the HLA allele is HLA-A*0201. In some embodiments, the binding proteins provided herein are genetically engineered, isolated, and / or purified. In some embodiments, the binding proteins have a higher binding affinity to the HA-2 peptide-MHC (pMHC) than does a known T-cell receptor (e.g., a TCR from van 15 Loenen et al. (2010) Proc. Natl. Acad. Sci. U.S.A. 107:10972-10977 or others described herein). For example, the binding proteins may have at least 1.2 fold, 1.5 fold, 1.8 fold, 2.0 fold, 2.2 fold, 2.5 fold, 2.8 fold, 3 fold, 3.5 fold, 4 fold, 4.5 fold, 5 fold, 5.5 fold, 6 fold, 6.5 fold, 7 fold, 7.5 fold, 8 fold, 8.5 fold, 9 fold, 9.5 fold, 10 fold, 11 fold, 12 fold, 13 fold, 14 fold, 15 fold, 16 fold, 17 fold, 18 fold, 19 fold, 20 fold, 25 fold, 30 fold, 35 fold, 40 fold, 45 20 fold, 50 fold, 60 fold, 70 fold, 80 fold, 90 fold, 100 fold, 1000 fold, 5000 fold, 10000 fold, 50000 fold, 100000 fold, 500000 fold, 1000000 fold, or more, or any range in between, inclusive, such as 1.2 fold to 2 fold, higher binding affinity to the HA-2 peptide-MHC (pMHC) than does a known T-cell receptor. In some embodiments, the binding protein induces higher T cell expansion, cytokine 25 release, and / or cytotoxic killing than does a known T-cell receptor when contacted with target cells with expression of HA-2 at a certain level or below (e.g., see Table 4 for representative cell lines expressing HA-2 at varying levels). For example, in some embodiments of any aspect described herein, HA-2 level can be expressed in terms of transcripts per million and may be, for example, less than or equal to about 1,000 transcript 30 per million transcripts (TPM), 950 TPM, 900 TPM, 850 TPM, 800 TPM, 750 TPM, 700 TPM, 650 TPM, 600 TPM, 550 TPM, 500 TPM, 450 TPM, 400 TPM, 350 TPM, 300 TPM, 250 TPM, 200 TPM, 150 TPM, 100 TPM, 95 TPM, 90 TPM, 85 TPM, 80 TPM, 75 TPM, 70 TPM, 65 TPM, 60 TPM, 55 TPM, 50 TPM, 45 TPM, 40 TPM, 35 TPM, 34 TPM, 33 2023204645   13 Jul 2023 TPM, 32 TPM, 31 TPM, 30 TPM, 29 TPM, 28 TPM, 27 TPM, 26 TPM, 25 TPM, 24 TPM, 23 TPM, 22 TPM, 21 TPM, 20 TPM, 19 TPM, 18 TPM, 17 TPM, 16 TPM, 15 TPM, 14 TPM, 13 TPM, 12 TPM, 11 TPM, 10 TPM, 9 TPM, 8 TPM, 7 TPM, 6 TPM, 5 TPM, 4 TPM, 3 TPM, 2 TPM, and 1 TPM, or any range in between, inclusive, such as less than or 5 equal to about 1,000 TPM to less than or equal to about 16 TPM). In some embodiments, the low HA-2 expression level is termed "heterozygous expression" meaning between about 1 TPM and about 35 TPM, or any range in between, inclusive, such as 32 TPM or 1-32 TPM. A higher expression is 36 TPM and higher. As described further herein, TPM is measured according to well-known techniques, such as RNA-Seq, and gene expression 10 TPM data are well known in the art for a variety of cell lines, tissue types, and the like (see, for example, the Broad Institute Cancer Cell Line Encyclopedia (CCLE) on the World Wide Web at portals.broadinstitute.org). In some embodiment, the binding protein induces at least 1.2 fold, 1.5 fold, 1.8 fold, 2.0 fold, 2.2 fold, 2.5 fold, 2.8 fold, 3 fold, 3.5 fold, 4 fold, 4.5 fold, 5 fold, 5.5 fold, 6 fold, 6.5 fold, 7 fold, 7.5 fold, 8 fold, 8.5 fold, 9 fold, 9.5 15 fold, 10 fold, 11 fold, 12 fold, 13 fold, 14 fold, 15 fold, 16 fold, 17 fold, 18 fold, 19 fold, 20 fold, 25 fold, 30 fold, 35 fold, 40 fold, 45 fold, 50 fold, 60 fold, 70 fold, 80 fold, 90 fold, 100 fold, 1000 fold, or more, or any range in between, inclusive, such as 1.2 fold to 2 fold, increase in T cell expansion, cytokine release, and / or cytotoxic killing than does a known T-cell receptor when contacted with target cells with heterozygous expression of HA-2. 20          In some embodiments, the expression of HA-2 is detected using RNA-sequencing (RNA-seq). RNA-seq generally comprises the following steps: obtaining a sample containing genetic material, isolating total RNA from the sample obtained, preparing an amplified cDNA library from the total RNA, sequencing the amplified cDNA library, and analyzing and profiling the amplified cDNA to assess the expression level of different 25 transcripts. The sample can be a population of cells, a tissue sample, a bioposy sample, a cell culture, or a single cell. Total RNA can be isolated from the biological sample using any method known in the art. In certain embodiments, total RNA is extracted from plasma. Plasma RNA extraction is described in Enders et al., “The Concentration of Circulating Corticotropin-Releasing Homer mRNA in Material Plasma Is Inclined in Preclampsia,” 30 Clinr. As described therein, the plasma collected after the centrifugation step is mixed with Trizol LS reagent (Invitrogen) and chloroform. The mixture is centrifuged and the aqueous layer is transferred to a new tube. Ethanol is added to this aqueous layer. The mixture is 2023204645   13 Jul 2023 then placed in an RNeasy mini column (Qiagen) and processed according to the manufacturer's recommendations. In some embodiments, RNA-seq described herein includes the step of preparing amplified cDNA from total RNA. For example, cDNA is prepared and the 5 isolated RNA sample is randomly amplified without dilution, or the mixture of genetic material in the isolated RNA is dispersed into individual reaction samples. In certain embodiments, amplification is initiated randomly at the 3 'end and throughout the entire transcriptome in the sample to amplify both mRNA and non-polyadenylated transcripts. In this way, double-stranded cDNA amplification products are optimized for the generation 10 of sequencing libraries for next generation sequencing platforms. A kit suitable for amplification of cDNA by the method encompassedy by the present invention includes, for example, Ovation® RNA-Seq System. In some embodiments, RNA-seq described herein includes the step of sequencing the amplified cDNA. Any known sequencing method can be used to 15 sequence the amplified cDNA mixture including the single molecule sequencing method. In certain embodiments, the amplified cDNA is sequenced by whole transcriptome shotgun sequencing. Whole transcriptome shotgun sequencing can be performed using various next generation sequencing platforms such as Illumina® Genome Analyzer platform, ABI SOLiD™ Sequencing platform, or Life Science's 454 Sequencing platform. 20          In some embodiments, RNA-seq described herein further comprises performing digital counting and analysis on the cDNA. The number of amplified sequences for each transcript in the amplified sample can be quantified by sequence reading (one reading per amplified strand). In some embodiments, transcript per million (TPM) is used to quantify the expression level of a particular transcript. TPM may be calculated as shown in Wagner 25 et al. (2012) Theory in Biosciences 131:281-285, the content of which is incorporated by reference herein in its entirety. In some embodiments, the binding proteins provided herein include (eg., comprise, consist essentially of, or consist of): a) a TCR alpha chain sequence with at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 30   95%, 96%, 97%, 98%, 99%, or more identity to a TCR alpha chain sequence selected from the group consisting of the TCR alpha sequences listed in Table 1; and / or b) a TCR beta chain sequence with at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identity to a TCR 2023204645   13 Jul 2023 beta chain sequence selected from the group consisting of the TCR beta chain sequences listed in Table 1. In some embodiments, the binding proteins provided herein include (e.g., comprise, consist essentially of, or consist of): a) a TCR alpha chain sequence selected from the group 5 consisting of the TCR alpha chain sequences listed in Table 1; and / or b) a TCR beta chain sequence selected from the group consisting of the TCR beta chain sequences listed in Table 1. In some embodiments, the binding proteins provided herein include (e.g., comprise, consist essentially of, or consist of): a) a TCR alpha chain variable (Va) domain sequence 10 with at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identity to a TCR alpha chain variable (Va) domain sequence selected from the group consisting of the TCR Va domain sequences listed in Table 1; and / or b) a TCR beta chain variable (Vp) domain sequence with at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 15   93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identity to a TCR beta chain variable (Vp) domain sequence selected from the group consisting of the TCR Vp domain sequences listed in Table 1. In some embodiments, the binding proteins provided herein include (e.g., comprise, consist essentially of, or consist of): a) a TCR alpha chain variable (Va) domain sequence 20 selected from the group consisting of the TCR Va domain sequences listed in Table 1; and / or b) a TCR beta chain variable (Vp) domain sequence selected from the group consisting of the TCR Vp domain sequences listed in Table 1. In some embodiments, the binding proteins provided herein include (e.g., comprise, consist essentially of, or consist of at least one (e.g., one, two or three, such as CDR3 alone 25 or in combination with a CDR1 and CDR2)) TCR alpha chain complementarity determining region (CDR) sequence with at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identity to a TCR alpha chain CDR sequence selected from the group consisting of the TCR alpha chain CDR sequences listed in Table 1. CDR3 is believed to be the main CDR 30 responsible for recognizing processed antigen and CDR1 and CDR2 mainly interact with the MHC, so, in some embodiments, binding protein comprising a CDR3 alone from a TCR alpha chain and / or a CDR3 alone from a TCR beta chain listed in Table 1, each CDR3 having a sequence homology as recited in this paragraph, are provided. 2023204645   13 Jul 2023 In some embodiments, the binding proteins provided herein may also include (e.g., comprise, consist essentially of, or consist of at least one (e.g., one, two or three, such as CDR3 alone or in combination with a CDR1 and CDR2)) TCR beta chain complementarity determining region (CDR) sequence with at least about 80%, 81%, 82%, 83%, 84%, 85%, 5   86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identity to a TCR beta chain CDR sequence selected from the group consisting of the TCR beta chain CDR sequences listed in Table 1. As described above, CDR3 is believed to be the main CDR responsible for recognizing processed antigen and CDR1 and CDR2 mainly interact with the MHC, so, in some embodiments, binding protein comprising a CDR3 10 alone from a TCR beta chain and / or a CDR3 alone from a TCR alpha chain listed in Table 1, each CDR3 having a sequence homology as recited in this paragraph, are provided. In some embodiments, the binding proteins provided herein include (e.g., comprise, consist essentially of, or consist of at least one (e.g., one, two or three)) TCR alpha chain complementarity determining region (CDR) listed in Table 1. 15          In some embodiments, the binding proteins provided herein may also include (e.g., comprise, consist essentially of, or consist of at least one (e.g., one, two or three)) TCR beta chain complementarity determining region (CDR) listed in Table 1. In some embodiments, the binding proteins provided herein include (e.g., comprise, consist essentially of, or consist of) a TCR alpha chain constant region (Ca) sequence with 20 at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identity to a TCR Ca sequence listed in Table 1. In some embodiments, the binding proteins provided herein may also include (e.g., comprise, consist essentially of, or consist of) a TCR beta chain constant region (Cp) 25 sequence with at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identity to a TCR Cp sequence listed in Table 1. In some embodiments, the binding proteins provided herein include (e.g., comprise, consist essentially of, or consist of) a TCR alpha chain constant region (Ca) sequence 30 selected from the group consisting of the TCR Ca sequences listed in Table 1. In some embodiments, the binding proteins provided herein may also include (e.g., comprise, consist essentially of, or consist of) a TCR beta chain constant region (Cp) sequence selected from the group consisting of the TCR Cp sequences listed in Table 1. 2023204645   13 Jul 2023 In some embodiments, the binding proteins provided herein comprise a constant region that is chimeric, humanized, human, primate, or rodent (e.g., rat or mouse). For example, a human variable region may be chimerized with a murine constant region or a murine variable region may be humanized with a human constant region and / or human 5 framework regions. In some embodiments, the constant regions may be mutated to modify functionality (e.g., introduction of non-naturally occurring cysteine substitutions in opposing residue locations in TCR alpha and beta chains to provide disulfide bonds useful for increasing affinity between the TCR alpha and beta chains). Similarly, mutations may be made in the transmembrane domain of the constant region to modify functionality (e.g., 10 increase hydrophobicity by introducing a non-naturally occurring substitution of a residue with a hydrophobic amino acid). In some embodiments, mutations may be made to the constant region to increase cell surface expression. Table 1 15 HA2-MJ1-DP1 wild type sequence: Alpha chain: TRAV34 / TRAJ42 / TRAC METVLOVLLGILGFOAAWVSSOELEOSPOSLIVQEGKNLTINCTSSKTLYGLYWYK OKYGEGLIFLMMLQKGGEEKSHEKITAKLDEKKOOSSLHITASOPRHAGIYLCGA 20 RKKNYGGSOGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitd ktvldmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnll mtlrlws Beta chain: 25 TRBV7-8 / TRBJ1-5 / TRBC1 MGTRLLCWVVLGFLGTDHTGAGVSQSPRYKVAKRGQDVALRCDPISGHVSLFWY OOALGOGPEFLTYFONEAQLDKSGLPSDRFFAERPEGSVSTLKIORTOOEDSAVYL CASSSGPTSPQHFGDGTRLSILEdlnkvtppevavfepseaeishtqkatlvclatgffpdhvelswwvngke vhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgfts 30 vsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ1-DP1 MGTM sequence: Alpha chain: TRAV34 / TRAJ42 / TRAC 35 METVLQVLLGILGFQAAWVSSQELEQSPQSLIVQEGKNLTINCTSSKTLYGLYWYK OKYGEGLIFLMMLOKGGEEKSHEKITAKLDEKKOQSSLHITASOPRHAGIYLCGA RKKNYGGSOGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitd ktvldmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnll mtlrlws 40 Beta chain: TRBV7-8 / TRBJ1 -5 / TRBC1 MGTRLLCWVVLGFLGTDHTGAGVSQSPRYKVAKRGQDVALRCDPISGHVSLFWY OOALGOGPEFLTYFONEAQLDKSGLPSDRFFAERPEGSVSTLKIORTOOEDSAVYL 2023204645   13 Jul 2023 CASSSGPTSPQHFGDGTRLSILEdlnkvfppevavfepskaeiahtqkatlvclatgffpdhvelswwvngke vhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgits asyhqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 5 HA2-MJ1-DP57 wild type sequence: Alpha chain: TRAV12-2 / TRAJ52 / TRAC MKSLRVLLVILWLOLSWVWSOQKEVEONSGPLSVPEGAIASLNCTYSDRGSOSFF WYROYSGKSPELIMFIYSNGDKEDGRFTAQLNKASOYVSLLIRDSOPSDSATYLCA 10 VNKGGGTSYGKLTFGQGTILTVHPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvyitd ktvldmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnll mtlrlws Beta chain: 15 TRBV27 / TRBJ1-1 / TRBC1 MGPQLLGYVVLCLLGAGPLEAQVTQNPRYLITVTGKKLTVTCSQNMNHEYMSWY RQDPGLGLRQIYYSMNVEVTDKGDVPEGYKVSRKEKRNFPLILESPSPNQTSLYFC ASSWTLNTEAFFGQGTRLTVVEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwvngk evhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgft 20 svsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ1-DP57 MGTM sequence: Alpha chain: TRAV 12-2 / TRAJ52 / TRAC 25 MKSLRVLLVILWLOLSWVWSOQKEVEONSGPLSVPEGAIASLNCTYSDRGSOSFF WYROYSGKSPELIMFIYSNGDKEDGRFTAQLNKASOYVSLLIRDSOPSDSATYLCA VNKGGGTSYGKLTFGQGTILTVHPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvyitd ktvldmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnll mtlrlws 30 Beta chain: TRBV27 / TRBJ1 - 1 / TRBC1 MGPOLLGYVVLCLLGAGPLEAOVTQNPRYLITVTGKKLTVTCSONMNHEYMSWY RODPGLGLROIYYSMNVEVTDKGDVPEGYKVSRKEKRNFPLILESPSPNOTSLYFC 35 ASSWTLNTEAFFGOGTRLTVVEdlnkvfppevavfepskaeiahtqkatlvclatgffpdhvelswwvngk evhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgit sasyhqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ1-DP2 wild type sequence: 40 Alpha chain: TRAV3 / TRAJ26 / TRAC MASAPISMLAMLFTLSGLRAOSVAOPEDQVNVAEGNPLTVKCTYSVSGNPYLFWY VOYPNRGLQFLLKYITGDNLVKGSYGFEAEFNKSOTSFHLKKPSALVSDSALYFCA VRDPGNYGQNFVFGPGTRLSVLPYiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvyitdkt 45 vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllm tlrlws Beta chain: TRBV7-9 / TRBJ2-5 / TRBC1 50 MGTSLLCWMALCLLGADHADTGVSODPRHKITKRGONVTFRCDPISEHNRLYWY 2023204645   13 Jul 2023 ROTLGOGPEFLTYFONEAQLEKSRLLSDRFSAERPKGSFSTLEIORTEOGDSAMYL CASSLLGHTOETQYFGPGTRLLVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwv ngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgrad cgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 5 HA2-MJ1-DP2 MGTM sequence: Alpha chain: TRAV3 / TRAJ26 / TRAC MASAPISMLAMLFTLSGLRAOSVAOPEDQVNVAEGNPLTVKCTYSVSGNPYLFWY 10 VQYPNRGLQFLLKYITGDNLVKGSYGFEAEFNKSQTSFHLKKPSALVSDSALYFCA VRDPGNYGQNFVFGPGTRLSVLPYiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdkt vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllm tlrlws 15 Beta chain: TRBV7-9 / TRBJ2-5 / TRBC1 MGTSLLCWMALCLLGADHADTGVSQDPRHKITKRGQNVTFRCDPISEHNRLYWY ROTLGOGPEFLTYFQNEAQLEKSRLLSDRFSAERPKGSFSTLEIQRTEOGDSAMYL CASSLLGHTQETQYFGPGTRLLVLEdlnkvfppevavfepskaeiahtqkatlvclatgffpdhvelsww 20 vngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgra dcgitsasyhqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ1-DP37 wild type sequence: Alpha chain: 25 TRAV36DV7 / TRAJ42 / TRAC MMKCPOALLAIFWLLLSWVSSEDKVVQSPLSLVVHEGDTVTLNCSYEVTNFRSLL WYKQEKKAPTFLFMLTSSGIEKKSGRLSSILDKKELFSILNITATQTGDSAIYLCAV EAGYGGSOGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdkt vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllm 30 tlrlws Beta chain: TRBV18 / TRB J1 -3 / TRBC1 MDTRLLCCAVICLLGAGLSNAGVMQNPRHLVRRRGOEARLRCSPMKGHSHVYW 35 YROLPEEGLKFMVYLQKENIIDESGMPKERFSAEFPKEGPSILRIOOVVRGDSAAYF CASSPRTGGIGNTIYFGEGSWLTVVEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelsww vngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgra dcgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 40 HA2-MJ1-DP37 MGTM sequence: Alpha chain: TRAV36DV7 / TRAJ42 / TRAC MMKCPOALLAIFWLLLSWVSSEDKVVQSPLSLVVHEGDTVTLNCSYEVTNFRSLL WYKQEKKAPTFLFMLTSSGIEKKSGRLSSILDKKELFSILNITATQTGDSAIYLCAV 45 EAGYGGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdkt vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllm tlrlws Beta chain: 50 TRBV 18 / TRBJ1 -3 / TRBC 1 2023204645   13 Jul 2023 MDTRLLCCAVICLLGAGLSNAGVMQNPRHLVRRRGOEARLRCSPMKGHSHVYW YRQLPEEGLKFMVYLQKENIIDESGMPKERFSAEFPKEGPSILRIOOVVRGDSAAYF CASSPRTGGIGNTIYFGEGSWLTVVEdlnkvfppevavfepskaeiahtqkatlvclatgflpdhvelsw wvngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawg 5   radcgitsasyhqgvlsatilye illgkatlyavlvsalvlmamvkrkdf HA2-MJ2-DP9 wild type sequence: Alpha chain: TRAV19 / TRAJ28 / TRAC 10 MLTASLLRAVIASICVVSSMAQKVTQAQTEISVVEKEDVTLDCVYETRDTTYYLF WYKQPPSGELVFLIRRNSFDEQNEISGRYSWNFOKSTSSFNFTITASQVVDSAVYFC ALSELAYSGAGSYOLTFGKGTKLSVIPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdv yitdktvldmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkva gfnllmtlrlws 15 Beta chain: TRBV11-2 / TRBJ2-3 / TRBC1 MGTRLLCWAALCLLGAELTEAGVAQSPRYKIIEKRQSVAFWCNPISGHATLYWYQ OILGOGPKLLIQFQNNGVVDDSOLPKDRFSAERLKGVDSTLKIQPAKLEDSAVYLC 20 ASSLOGLPDTDTOYFGPGTRLTVLEdlnkvfppevavfepseaeishtqkatlvclatgffodhvelswwv ngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgrad cgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ2-DP9 MGTM sequence: 25 Alpha chain: TRAV 19 / TRAJ28 / TRAC MLTASLLRAVIASICVVSSMAQKVTQAQTEISVVEKEDVTLDCVYETRDTTYYLF WYKOPPSGELVFLIRRNSFDEQNEISGRYSWNFOKSTSSFNFTITASOWDSAVYFC ALSELAYSGAGSYQLTFGKGTKLSVIPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdv 30 yitdktvldmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkva gfnllmtlrlws Beta chain: TRBV11-2 / TRBJ2-3 / TRBC1 35 MGTRLLCWAALCLLGAELTEAGVAOSPRYKIIEKROSVAFWCNPISGHATLYWYQ OILGOGPKLLIQFONNGVVDDSOLPKDRFSAERLKGVDSTLKIOPAKLEDSAVYLC ASSLOGLPDTDTOYFGPGTRLTVLEdlnkvfppevavfepskaeiahtqkatlvclatgffpdhvelswwv ngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgrad cgitsasyhqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 40 HA2-MJ2-DP25 wild type sequence: Alpha chain: TRAV21 / TRAJ42 / TRAC METLLGLLILWLQLQWVSSKQEVTQIPAALSVPEGENLVLNCSFTDSAIYNLQWFR 45 ODPGKGLTSLLLIQSSOREOTSGRLNASLDKSSGRSTLYIAASOPGDSATYLCAVRS GYGGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvld mrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllmtlrl ws 50 Beta chain: 2023204645   13 Jul 2023 TRBV7-8 / TRBJ2-5 / TRBC1 MGTRLLCWVVLGFLGTDHTGAGVSOSPRYKVAKRGODVALRCDPISGHVSLFWY OOALGOGPEFLTYFONEAQLDKSGLPSDRFFAERPEGSVSTLKIORTOOEDSAVYL CASSFSGSTOETQYFGPGTRLLVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwv 5 ngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgrad cgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ2-DP25 MGTM sequence: Alpha chain: 10 TRAV21 / TRAJ42 / TRAC METLLGLLILWLQLQWVSSKQEVTQIPAALSVPEGENLVLNCSFTDSAIYNLQWFR ODPGKGLTSLLLIQSSOREOTSGRLNASLDKSSGRSTLYIAASOPGDSATYLCAVRS GYGGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvld mrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllmtlrl 15 ws Beta chain: TRBV7-8 / TRBJ2-5 / TRBC1 MGTRLLCWVVLGFLGTDHTGAGVSQSPRYKVAKRGQDVALRCDPISGHVSLFWY 20 OOALGOGPEFLTYFONEAQLDKSGLPSDRFFAERPEGSVSTLKIORTOOEDSAVYL CASSFSGSTQETQYFGPGTRLLVLEdlnkvfppevavfepskaeiahtqkatlvclatgffpdhvelswwv ngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgrad cgitsasyhqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 25 HA2-MJ2-DP17 wild type sequence: Alpha chain: TRAV21 / TRAJ42 / TRAC METLLGLLILWLOLOWVSSKOEVTOIPAALSVPEGENLVLNCSFTDSAIYNLQWFR ODPGKGLTSLLLIQSSOREOTSGRLNASLDKSSGRSTLYIAASOPGDSATYLCAVR 30 WGYGGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvyitdktv Idmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllmtl rlws Beta chain: 35 TRBV7-8 / TRBJ2-3 / TRBC1 MGTRLLCWVVLGFLGTDHTGAGVSQSPRYKVAKRGQDVALRCDPISGHVSLFWY OOALGOGPEFLTYFONEAQLDKSGLPSDRFFAERPEGSVSTLKIORTOOEDSAVYL CASSSSAGFTDTQYFGPGTRLTVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwv ngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgrad 40 cgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ2-DP17 MGTM sequence: Alpha chain: TRAV21 / TRAJ42 / TRAC 45 METLLGLLILWLOLOWVSSKOEVTOIPAALSVPEGENLVLNCSFTDSAIYNLQWFR ODPGKGLTSLLLIQSSOREOTSGRLNASLDKSSGRSTLYIAASOPGDSATYLCAVR WGYGGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktv Idmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllmtl rlws 50 2023204645   13 Jul 2023 Beta chain: TRBV7-8 / TRBJ2-3 / TRBC1 MGTRLLCWVVLGFLGTDHTGAGVSOSPRYKVAKRGODVALRCDPISGHVSLFWY OOALGOGPEFLTYFONEAQLDKSGLPSDRFFAERPEGSVSTLKIORTOOEDSAVYL 5 CASSSSAGFTDTQYFGPGTRLTVLEdlnkvfppevavfepskaeiahtqkatlvclatgffpdhvelswwv ngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgrad cgitsasyhqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ1-DP33 wild type sequence: 10 Alpha chain: TRAV35 / TRAJ42 / TRAC MLLEHLLIILWMQLTWVSGQQLNQSPQSMFIQEGEDVSMNCTSSSIFNTWLWYKQ EPGEGPVLLIALYKAGELTSNGRLTAQFGITRKDSFLNISASIPSDVGIYFCAGPPM NYGGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvld 15 mrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllmtlrl ws Beta chain: TRBV7-8 / TRBJ2-1 / TRBC1 20 MGTRLLCWVVLGFLGTDHTGAGVSOSPRYKVAKRGODVALRCDPISGHVSLFWY OQALGOGPEFLTYFQNEAQLDKSGLPSDRFFAERPEGSVSTLKIQRTOQEDSAVYL CASSLFSRHEQFFGPGTRLTVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwvngk evhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgft svsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 25 HA2-MJ1-DP33 MGTM sequence: Alpha chain: TRAV35 / TRAJ42 / TRAC MLLEHLLIILWMQLTWVSGQQLNQSPQSMFIQEGEDVSMNCTSSSIFNTWLWYKQ 30 EPGEGPVLLIALYKAGELTSNGRLTAQFGITRKDSFLNISASIPSDVGIYFCAGPPM NYGGSOGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvld mrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllmtlrl ws 35 Beta chain: TRBV7-8 / TRBJ2-1 / TRBC1 MGTRLLCWVVLGFLGTDHTGAGVSOSPRYKVAKRGODVALRCDPISGHVSLFWY OOALGOGPEFLTYFONEAQLDKSGLPSDRFFAERPEGSVSTLKIORTOOEDSAVYL CASSLFSRHEQFFGPGTRLTVLEdlnkvfppevavfepskaeiahtqkatlvclatgffpdhvelswwvngk 40 evhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgit sasyhqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ3-DP12 wild type sequence: Alpha chain: 45 TRAV27 / TRAJ42 / TRAC MVLKFSVSILWIQLAWVSTQLLEQSPQFLSIQEGENLTVYCNSSSVFSSLQWYRQEP GEGPVLLVTVVTGGEVKKLKRLTFQFGDARKDSSLHITAAQTGDTGLYLCAGAG MNYGGSOGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvl dmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllmtlr 50 Iws 2023204645   13 Jul 2023 Beta chain: TRBV18 / TRBJ2- 1 / TRBC1 MDTRLLCCAVICLLGAGLSNAGVMQNPRHLVRRRGOEARLRCSPMKGHSHVYW 5 YRQLPEEGLKFMVYLQKENIIDESGMPKERFSAEFPKEGPSILRIQQVVRGDSAAYF CASSLTSGRLNEQFFGPGTRLTVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwv ngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgrad cgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 10 HA2-MJ3-DP12 MGTM sequence: Alpha chain: TRAV27 / TRAJ42 / TRAC MVLKFSVSILWIQLAWVSTQLLEQSPQFLSIQEGENLTVYCNSSSVFSSLQWYRQEP GEGPVLLVTVVTGGEVKKLKRLTFOFGDARKDSSLHITAAQTGDTGLYLCAGAG 15 MNYGGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvl dmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllmtlr Iws Beta chain: 20 TRBV 18 / TRBJ2-1 / TRBC 1 MDTRLLCCAVICLLGAGLSNAGVMQNPRHLVRRRGQEARLRCSPMKGHSHVYW YRQLPEEGLKFMVYLQKENIIDESGMPKERFSAEFPKEGPSILRIOQVVRGDSAAYF CASSLTSGRLNEQFFGPGTRLTVLEdlnkvfppevavfepskaeiahtqkatlvclatgffpdhvelswwv ngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgrad 25 cgitsasyhqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ3-DP20 wild type sequence: Alpha chain: 30 TRAV39 / TRAJ42 / TRAC MKKLLAMILWLOLDRLSGELKVEONPLFLSMQEGKNYTIYCNYSTTSDRLYWYR ODPGKSLESLFVLLSNGAVKQEGRLMASLDTKARLSTLHITAAVHDLSATYFCAV PMGYGGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvyitdkt vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllm 35 tlrlws Beta chain: TRBV7-8 / TRBJ2-5 / TRBC1 MGTRLLCWVVLGFLGTDHTGAGVSQSPRYKVAKRGQDVALRCDPISGHVSLFWY 40 OOALGOGPEFLTYFONEAQLDKSGLPSDRFFAERPEGSVSTLKIORTOOEDSAVYL CASSRGPGTQYFGPGTRLLVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwvngke vhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgfts vsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 45 HA2-MJ3-DP20 MGTM sequence: Alpha chain: TRAV39 / TRAJ42 / TRAC MKKLLAMILWLOLDRLSGELKVEONPLFLSMQEGKNYTIYCNYSTTSDRLYWYR QDPGKSLESLFVLLSNGAVKQEGRLMASLDTKARLSTLHITAAVHDLSATYFCAV 5 0  PM GY GGSQGNLIFGKGTKL S VKPN iqnpdpavyqlrdskssdksvc Iftdfdsqtnvsqskdsdvyitdkt 2023204645   13 Jul 2023 vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllm tlrlws Beta chain: 5 TRBV7-8 / TRBJ2-5 / TRBC1 MGTRLLCWVVLGFLGTDHTGAGVSQSPRYKVAKRGQDVALRCDPISGHVSLFWY OOALGOGPEFLTYFONEAQLDKSGLPSDRFFAERPEGSVSTLKIORTOOEDSAVYL CASSRGPGTOYFGPGTRLLVLEdlnkvfppevavfepskaeiahtqkatlvclatgffpdhvelswwvngke vhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgits 10 asyhqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-BG3-DP15 wild type sequence: Alpha chain: TRAV21 / TRAJ42 / TRAC 15 METLLGLLILWLQLQWVSSKQEVTQIPAALSVPEGENLVLNCSFTDSAIYNLQWFR ODPGKGLTSLLLIQSSQREQTSGRLNASLDKSSGRSTLYIAASOPGDSATYLCAVR PGDYGGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdkt vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllm tlrlws 20 Beta chain: TRBV7-8 / TRBJ2-5 / TRBC1 MGTRLLCWVVLGFLGTDHTGAGVSQSPRYKVAKRGQDVALRCDPISGHVSLFWY OOALGOGPEFLTYFONEAQLDKSGLPSDRFFAERPEGSVSTLKIORTOOEDSAVYL 25 CASSFFOGETOYFGPGTRLLVLEdlnkvfppevavfepseaeishtqkatlvclatgffbdhvelswwvngk evhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgft svsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-BG3-DP15 MGTM sequence: 30 Alpha chain: TRAV21 / TRAJ42 / TRAC METLLGLLILWLQLQWVSSKQEVTQIPAALSVPEGENLVLNCSFTDSAIYNLQWFR ODPGKGLTSLLLIQSSOREOTSGRLNASLDKSSGRSTLYIAASOPGDSATYLCAVR PGDYGGSOGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdkt 35 vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllm tlrlws Beta chain: TRBV7-8 / TRBJ2-5 / TRBC1 40 MGTRLLCWVVLGFLGTDHTGAGVSOSPRYKVAKRGODVALRCDPISGHVSLFWY OQALGOGPEFLTYFQNEAQLDKSGLPSDRFFAERPEGSVSTLKIQRTOQEDSAVYL CASSFFOGETQYFGPGTRLLVLEdlnkvfppevavfepskaeiahtqkatlvclatgffpdhvelswwvng kevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgi tsasyhqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 45 HA2-BG3-DP42 wild type sequence: Alpha chain: TRA V6 / TRA J13 / TRAC MAFWLRSLGLHFRPHLGRRMESFLGGVLLILWLQVDWVKSQKIEQNSEALNIQEG 50 KTATLTCNYTNYSPAYLOWYRODPGRGPVFLLLIRENEKEKRKERLKVTFDTTLK 2023204645   13 Jul 2023 QSLFHITASQPADSATYLCALVGGGYQKVTFGTGTKLQVIPNiqnpdpavyqlrdskssdks vclftdfdsqtnvsqskdsdvyitdktvldmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfet dtnlnfqnlsvigfrilllkvagfnllmtlrlws 5 Beta chain: TRBV6-2 / TRBJ2-1 / TRBC1 MSLGLLCCGAFSLLWAGPVNAGVTOTPKFRVLKTGOSMTLLCAQDMNHEYMYW YRODPGMGLRLIHYSVGEGTTAKGEVPDGYNVSRLKKQNFLLGLESAAPSOTSVY FCATLTERSSYNEOFFGPGTRLTVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelsww 10 vngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgra dcgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-BG3-DP42 MGTM sequence: Alpha chain: 15 TRAV6 / TRAJ13 / TRAC MAFWLRSLGLHFRPHLGRRMESFLGGVLLILWLQVDWVKSQKIEQNSEALNIQEG KTATLTCNYTNYSPAYLQWYRQDPGRGPVFLLLIRENEKEKRKERLKVTFDTTLK OSLFHITASOPADSATYLCALVGGGYQKVTFGTGTKLOVIPNiqnpdpavyqlrdskssdks vclftdfdsqtnvsqskdsdvyitdktvldmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfe 20 tdtnlnfqnllvivlrilllkvagfnllmtlrlws Beta chain: TRBV6-2 / TRBJ2-1 / TRBC1 MSLGLLCCGAFSLLWAGPVNAGVTOTPKFRVLKTGOSMTLLCAQDMNHEYMYW 25 YRODPGMGLRLIHYSVGEGTTAKGEVPDGYNVSRLKKQNFLLGLESAAPSOTSVY FCATLTERSSYNEOFFGPGTRLTVLEdlnkvfppevavfepskaeiahtqkatlvclatgffpdhvelsww vngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgra dcgitsasyhqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 30 HA2-BG3-DP67 wild type sequence: Alpha chain: TRAV26-1 / TRAJ42 / TRAC MRLVARVTVFLTFGTIIDAKTTOPTSMDCAEGRAANLPCNHSTISGNEYVYWYRQI HSOGPOYIIHGLKNNETNEMASLIITEDRKSSTLILPHATLRDTAVYYCIVRPRNYG 35 GSOGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvldmrsm dfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllmtlrlws Beta chain: TRBV7-9 / TRBJ1 -4 / TRBC1 40 MGTSLLCWMALCLLGADHADTGVSODPRHKITKRGQNVTFRCDPISEHNRLYWY ROTLGOGPEFLTYFQNEAQLEKSRLLSDRFSAERPKGSFSTLEIQRTEOGDSAMYL CASSLDFDLGQTRRANEKLFFGSGTOLSVLEdlnkvfppevavfepseaeishtqkatlvclatgffpd hvelswwvngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivs aeawgradcgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 45 HA2-BG3-DP67 MGTM sequence: Alpha chain: TRAV26-1 / TRAJ42 / TRAC MRLVARVTVFLTFGTIIDAKTTQPTSMDCAEGRAANLPCNHSTISGNEYVYWYRQI 50 HSOGPOYIIHGLKNNETNEMASLIITEDRKSSTLILPHATLRDTAVYYCIVRPRNYG 2023204645   13 Jul 2023 GSOGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvldmrsm dfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllmtlrlws Beta chain: 5 TRBV7-9 / TRBJ1-4 / TRBC1 MGTSLLCWMALCLLGADHADTGVSQDPRHKITKRGQNVTFRCDPISEHNRLYWY RQTLGOGPEFLTYFONEAQLEKSRLLSDRFSAERPKGSFSTLEIORTEOGDSAMYL CASSLDFDLGQTRRANEKLFFGSGTOLSVLEdlnkvfppevavfepskaeiahtqkatlvclatgffp dhvelswwvngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqi 10 vsaeawgradcgitsasyhqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ2-DP8 wild type sequence (same CDRs as “TCR-101a”): Alpha chain: TRAV41 / TRAJ50 / TRAC 15 MVKIRQFLLAILWLQLSCVSAAKNEVEQSPQNLTAQEGEFITINCSYSVGISALHWL QQHPGGGIVSLFMLSSGKKKHGRLIATINIQEKHSSLHITASHPRDSAVYICAVDGT GGTKKTSYDKVIFGPGTSLSVIPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvyitdktvl dmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllmtlr Iws 20 Beta chain: TRBV5-1 / TRBJ2-1 / TRBC1 MGSRLLCWVLLCLLGAGPVKAGVTQTPRYLIKTRGQQVTLSCSPISGHRSVSWYQ OTPGOGLOFLFEYFSETQRNKGNFPGRFSGROFSNSRSEMNVSTLELGDSALYLCA 25 SSLRGLAAYNEQFFGPGTRLTVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwvn gkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgradc gftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ2-DP8 MGTM sequence (also known as “TCR-101a”): 30 Alpha chain: TRAV41 / TRAJ50 / TRAC MVKIRQFLLAILWLQLSCVSAAKNEVEQSPQNLTAQEGEFITINCSYSVGISALHWL QQHPGGGIVSLFMLSSGKKKHGRLIATINIQEKHSSLHITASHPRDSAVYICAVDGT GGTKKTSYDKVIFGPGTSLSVIPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvl 35 dmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllmtlr Iws Beta chain: TRBV5-1 / TRBJ2-1 / TRBC1 40 MGSRLLCWVLLCLLGAGPVKAGVTQTPRYLIKTRGQQVTLSCSPISGHRSVSWYQ OTPGOGLOFLFEYFSETQRNKGNFPGRFSGRQFSNSRSEMNVSTLELGDSALYLCA SSLRGLAAYNEQFFGPGTRLTVLEdlnkvfppevavfepskaeiahtqkatlvclatgffpdhvelswwvn gkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgradc gitsasyhqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 45 HA2-MJ7-DP19 wild type sequence (same CDRs as “TCR-101b”): Alpha chain: TRAV39 / TRAJ43 / TRAC MKKLLAMILWLQLDRLSGELKVEQNPLFLSMQEGKNYTIYCNYSTTSDRLYWYR 50 QDPGKSLESLFVLLSNGAVKOEGRLMASLDTKARLSTLHITAAVHDLSATYFCAV 2023204645   13 Jul 2023 DTNMRFGAGTRLTVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvyitdktvldmrsmdfk snsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllmtlrlws Beta chain: 5 TRBV6-1 / TRBJ1-4 / TRBC1 MSIGLLCCVAFSLLWASPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHNSMYW YRQDPGMGLRLIYYSASEGTTDKGEVPNGYNVSRLNKREFSLRLESAAPSQTSVYF CASSEIOGEKLFFGSGTOLSVLEdlnkvfppevavfepseaeishtqkatlvclatgffodhvelswwvngk evhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgft 10 svsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ7-DP19 MGTM sequence (also known as “TCR-101b”): Alpha chain: TRAV39 / TRAJ43 / TRAC 15 MKKLLAMILWLQLDRLSGELKVEQNPLFLSMQEGKNYTIYCNYSTTSDRLYWYR QDPGKSLESLFVLLSNGAVKQEGRLMASLDTKARLSTLHITAAVHDLSATYFCAV DTNMRFGAGTRLTVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvyitdktvldmrsmdfk snsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllmtlrlws 20 Beta chain: TRBV6-1 / TRBJ1-4 / TRBC1 MSIGLLCCVAFSLLWASPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHNSMYW YRQDPGMGLRLIYYSASEGTTDKGEVPNGYNVSRLNKREFSLRLESAAPSQTSVYF CASSEIQGEKLFFGSGTOLSVLEdlnkvfppevavfepskaeiahtqkatlvclatgffbdhvelswwvngk 25 evhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgit sasyhqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ2-DP1 wild type sequence: Alpha chain: 30 TRAV39 / TRAJ42 / TRAC MKKLLAMILWLOLDRLSGELKVEONPLFLSMQEGKNYTIYCNYSTTSDRLYWYR ODPGKSLESLFVLLSNGAVKQEGRLMASLDTKARLSTLHITAAVHDLSATYFCAV RMGYGGSOGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdkt vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllm 35 tlrlws Beta chain: TRBV7-8 / TRBJ1 -5 / TRBC1 MGTRLLCWVVLGFLGTDHTGAGVSQSPRYKVAKRGQDVALRCDPISGHVSLFWY 40 OOALGOGPEFLTYFONEAQLDKSGLPSDRFFAERPEGSVSTLKIORTOOEDSAVYL CASSFASQPQHFGDGTRLSILEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwvngkev hsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgftsv syqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 45 HA2-MJ2-DP1 MGTM sequence: Alpha chain: TRAV39 / TRAJ42 / TRAC MKKLLAMILWLOLDRLSGELKVEONPLFLSMQEGKNYTIYCNYSTTSDRLYWYR QDPGKSLESLFVLLSNGAVKQEGRLMASLDTKARLSTLHITAAVHDLSATYFCAV 50 RMGYGGSOGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdkt 2023204645   13 Jul 2023 vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllm tlrlws Beta chain: 5 TRBV7-8 / TRBJ1-5 / TRBC1 MGTRLLCWVVLGFLGTDHTGAGVSQSPRYKVAKRGQDVALRCDPISGHVSLFWY OOALGOGPEFLTYFONEAQLDKSGLPSDRFFAERPEGSVSTLKIORTOOEDSAVYL CASSFASOPOHFGDGTRLSILEdlnkvfppevavfepskaeiahtqkatlvclatgffpdhvelswwvngkev hsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgitsa 10 syhqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ13-DP32 sequence: Alpha chain: TRAV22 / TRAJ26 / TRAC 15 MKRILGALLGLLSAQVCCVRGIQVEQSPPDLILQEGANSTLRCNFSDSVNNLQWFH QNPWGQLINLFYIPSGTKQNGRLSATTVATERYSLLYISSSQTTDSGVYFCAVEGG SYNYGQNFVFGPGTRLSVLPYiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvldmr smdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllmtlrlws 20 Beta chain: TRBV7-9 / TRBJ2-1 / TRBC1 MGTSLLCWMALCLLGADHADTGVSQDPRHKITKRGQNVTFRCDPISEHNRLYWY ROTLGOGPEFLTYFQNEAQLEKSRLLSDRFSAERPKGSFSTLEIQRTEOGDSAMYL CASSLVRERERGNEQFFGPGTRLTVLEdlnkvfppevavfepseaeishtqkatlvclatgffbdhvels 25 wwvngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeaw gradcgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ13-DP32 MGTM Sequence: Alpha chain: 30 TRAV22 / TRAJ26 / TRAC MKRILGALLGLLSAOVCCVRGIOVEOSPPDLILOEGANSTLRCNFSDSVNNLQWFH ONPWGOLINLFYIPSGTKQNGRLSATTVATERYSLLYISSSOTTDSGVYFCAVEGG SYNYGONFVFGPGTRLSVLPYiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvyitdktvldmr smdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllmtlrlws 35 Beta chain: TRBV7-9 / TRBJ2-1 / TRBC1 MGTSLLCWMALCLLGADHADTGVSODPRHKITKRGONVTFRCDPISEHNRLYWY ROTLGOGPEFLTYFQNEAQLEKSRLLSDRFSAERPKGSFSTLEIQRTEOGDSAMYL 40 CASSLVRERERGNEQFFGPGTRLTVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvels wwvngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeaw gradcgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ13-DP148 sequence: 45 Alpha chain: TRAV21 / TRAJ42 / TRAC METLLGLLILWLQLQWVSSKQEVTQIPAALSVPEGENLVLNCSFTDSAIYNLQWFR ODPGKGLTSLLLIOSSOREQTSGRLNASLDKSSGRSTLYIAASOPGDSATYLCAVR VRDYGGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdkt 50 vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllm 2023204645   13 Jul 2023 tlrlws Beta chain: TRBV18 / TRB J1 -4 / TRBC1 5 MDTRLLCCAVICLLGAGLSNAGVMQNPRHLVRRRGQEARLRCSPMKGHSHVYW YRQLPEEGLKFMVYLQKENIIDESGMPKERFSAEFPKEGPSILRIQQVVRGDSAAYF CASSPPGGQGEKLFFGSGTQLSVLEdlnkvlppevavfepseaeishtqkatlvclatgffpdhvelswwv ngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgrad cgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 10 HA2-MJ13-DP148 MGTM Sequence: Alpha chain: TRAV21 / TRAJ42 / TRAC METLLGLLILWLQLQWVSSKQEVTQIPAALSVPEGENLVLNCSFTDSAIYNLQWFR 15 ODPGKGLTSLLLIQSSOREOTSGRLNASLDKSSGRSTLYIAASOPGDSATYLCAVR VRDYGGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdkt vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllm tlrlws 20 Beta chain: TRBV 18 / TRB J1 -4 / TRBC 1 MDTRLLCCAVICLLGAGLSNAGVMQNPRHLVRRRGQEARLRCSPMKGHSHVYW YRQLPEEGLKFMVYLQKENIIDESGMPKERFSAEFPKEGPSILRIOQVVRGDSAAYF CASSPPGGOGEKLFFGSGTOLSVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwv 25 ngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgrad cgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ13-SP43 sequence: Alpha chain: 30 TRAV12-2 / TRAJ11 / TRAC MKSLRVLLVILWLOLSWVWSOQKEVEONSGPLSVPEGAIASLNCTYSDRGSOSFF WYROYSGKSPELIMFIYSNGDKEDGRFTAQLNKASOYVSLLIRDSOPSDSATYLCA VKGAGYSTLTFGKGTMLLVSPDiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvyitdktvld mrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllmtlrl 35 ws Beta chain: TRBV6-5 / TRBJ2-3 / TRBC1 MSIGLLCCAALSLLWAGPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHEYMSW 40 YRODPGMGLRLIHYSVGAGITDQGEVPNGYNVSRSTTEDFPLRLLSAAPSOTSVYF CASSDGGALAYFGPGTRLTVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwvngke vhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgfts vsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 45  HA2-MJ13-SP43 MGTM Sequence: Alpha chain: TRAV12-2 / TRAJ11 / TRAC MKSLRVLLVILWLOLSWVWSOQKEVEONSGPLSVPEGAIASLNCTYSDRGSOSFF WYRQYSGKSPELIMFIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCA 50 VKGAGYSTLTFGKGTMLLVSPDiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvld 2023204645   13 Jul 2023 mrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllmtlrl ws Beta chain: 5 TRBV6-5 / TRBJ2-3 / TRBC1 MSIGLLCCAALSLLWAGPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHEYMSW YRODPGMGLRLIHYSVGAGITDQGEVPNGYNVSRSTTEDFPLRLLSAAPSOTSVYF CASSDGGALAYFGPGTRLTVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwvngke vhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgfts 10 vsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ14-DP33 sequence: Alpha chain: TRAV36DV7 / TRAJ42 / TRAC 15 MMKCPQALLAIFWLLLSWVSSEDKVVQSPLSLVVHEGDTVTLNCSYEVTNFRSLL WYKQEKKAPTFLFMLTSSGIEKKSGRLSSILDKKELFSILNITATQTGDSAIYLCAV ESGYGGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktv Idmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllmtl rlws 20 Beta chain: TRBV18 / TRB J1 -3 / TRBC1 MDTRLLCCAVICLLGAGLSNAGVMQNPRHLVRRRGQEARLRCSPMKGHSHVYW YROLPEEGLKFMVYLQKENIIDESGMPKERFSAEFPKEGPSILRIOOVVRGDSAAYF 25 CASSPRTGGDGNTIYFGEGSWLTWEdlnkvfppevavfepseaeishtqkatlvclatgffbdhvelsw wvngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawg radcgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ14-DP33 MGTM Sequence: 30 Alpha chain: TRAV36DV7 / TRAJ42 / TRAC MMKCPQALLAIFWLLLSWVSSEDKVVQSPLSLVVHEGDTVTLNCSYEVTNFRSLL WYKQEKKAPTFLFMLTSSGIEKKSGRLSSILDKKELFSILNITATQTGDSAIYLCAV ESGYGGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktv 35 Idmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllmtl rlws Beta chain: TRBV 18 / TRB J1 -3 / TRBC 1 40 MDTRLLCCAVICLLGAGLSNAGVMQNPRHLVRRRGOEARLRCSPMKGHSHVYW YRQLPEEGLKFMVYLQKENIIDESGMPKERFSAEFPKEGPSILRIOQVVRGDSAAYF CASSPRTGGDGNTIYFGEGSWLTWEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelsw wvngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawg radcgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 45 HA2-MJ14-DP45 sequence: Alpha chain: TRAV20 / TRAJ42 / TRAC MEKMLECAFIVLWLQLGWLSGEDQVTQSPEALRLQEGESSSLNCSYTVSGLRGLF 50 WYRODPGKGPEFLFTLYSAGEEKEKERLKATLTKKESFLHITAPKPEDSATYLCAV 2023204645   13 Jul 2023 OASYGGSOGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdkt vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllm tlrlws 5 Beta chain: TRBV18 / TRBJ2-5 / TRBC1 MDTRLLCCAVICLLGAGLSNAGVMQNPRHLVRRRGOEARLRCSPMKGHSHVYW YRQLPEEGLKFMVYLQKENIIDESGMPKERFSAEFPKEGPSILRIOOVVRGDSAAYF CASSPVPVPLPTTOETQYFGPGTRLLVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvel 10 swwvngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaea wgradcgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ14-DP45 MGTM Sequence: Alpha chain: 15 TRAV20 / TRAJ42 / TRAC MEKMLECAFIVLWLQLGWLSGEDQVTQSPEALRLQEGESSSLNCSYTVSGLRGLF WYRQDPGKGPEFLFTLYSAGEEKEKERLKATLTKKESFLHITAPKPEDSATYLCAV QASYGGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvyitdkt vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllm 20 tlrlws Beta chain: TRBV 18 / TRBJ2-5 / TRBC1 MDTRLLCCAVICLLGAGLSNAGVMQNPRHLVRRRGOEARLRCSPMKGHSHVYW 25 YROLPEEGLKFMVYLQKENIIDESGMPKERFSAEFPKEGPSILRIOOVVRGDSAAYF CASSPVPVPLPTTOETQYFGPGTRLLVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvel swwvngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaea wgradcgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 30  HA2-MJ14-DP137 sequence: Alpha chain: TRAV27 / TRAJ42 / TRAC MVLKFSVSILWIOLAWVSTOLLEOSPOFLSIOEGENLTVYCNSSSVFSSLOWYRQEP GEGPVLLVTVVTGGEVKKLKRLTFOFGDARKDSSLHITAAOTGDTGLYLCAGAPS 35 NYGGSOGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvld mrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllmtlrl ws Beta chain: 40 TRBV18 / TRBJ2-1 / TRBC1 MDTRLLCCAVICLLGAGLSNAGVMQNPRHLVRRRGQEARLRCSPMKGHSHVYW YROLPEEGLKFMVYLQKENIIDESGMPKERFSAEFPKEGPSILRIOOVVRGDSAAYF CASSPPGONNEOFFGPGTRLTVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwvn gkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgradc 45 gftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ14-DP137 MGTM Sequence: Alpha chain: TRAV27 / TRAJ42 / TRAC 50 MVLKFSVSILWIOLAWVSTOLLEOSPOFLSIOEGENLTVYCNSSSVFSSLOWYRQEP 2023204645   13 Jul 2023 GEGPVLLVTVVTGGEVKKLKRLTFOFGDARKDSSLHITAAQTGDTGLYLCAGAPS NYGGSOGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvld mrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllmtlrl ws 5 Beta chain: TRBV18 / TRBJ2- 1 / TRBC1 MDTRLLCCAVICLLGAGLSNAGVMQNPRHLVRRRGOEARLRCSPMKGHSHVYW YROLPEEGLKFMVYLQKENIIDESGMPKERFSAEFPKEGPSILRIOOVVRGDSAAYF 10 CASSPPGONNEQFFGPGTRLTVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwvn gkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgradc gftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ14-SP4 sequence: 15 Alpha chain: TRAV12-2 / TRAJ11 / TRAC MKSLRVLLVILWLOLSWVWSOQKEVEQNSGPLSVPEGAIASLNCTYSDRGSQSFF WYRQYSGKSPELIMFIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCA VRRSGYSTLTFGKGTMLLVSPDiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvyitdktvld 20 mrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllmtlrl ws Beta chain: TRBV6-5 / TRBJ1-1 / TRBC 1 25 MSIGLLCCAALSLLWAGPVNAGVTOTPKFOVLKTGOSMTLOCAQDMNHEYMSW YRQDPGMGLRLIHYSVGAGITDOGEVPNGYNVSRSTTEDFPLRLLSAAPSQTSVYF CASSLGAEAFFGQGTRLTVVEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwvngkev hsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgftsv syqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 30 HA2-MJ14-SP4 MGTM Sequence: Alpha chain: TRAV12-2 / TRAJ11 / TRAC MKSLRVLLVILWLOLSWVWSOQKEVEONSGPLSVPEGAIASLNCTYSDRGSOSFF 35 WYROYSGKSPELIMFIYSNGDKEDGRFTAQLNKASOYVSLLIRDSOPSDSATYLCA VRRSGYSTLTFGKGTMLLVSPDiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvld mrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllmtlrl ws 40 Beta chain: TRBV6-5 / TRBJ1-1 / TRBC 1 MSIGLLCCAALSLLWAGPVNAGVTOTPKFOVLKTGOSMTLOCAQDMNHEYMSW YRODPGMGLRLIHYSVGAGITDQGEVPNGYNVSRSTTEDFPLRLLSAAPSOTSVYF CASSLGAEAFFGQGTRLTVVEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwvngkev 45 hsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgftsv syqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ14-DP162 sequence: Alpha chain: 50 TRAV8-2 / TRAJ42 / TRAC 2023204645   13 Jul 2023 MLLLLVPVLEVIFTLGGTRAOSVTQLDSHVSVSEGTPVLLRCNYSSSYSPSLFWYV OHPNKGLQLLLKYTSAATLVKGINGFEAEFKKSETSFHLTKPSAHMSDAAEYFCV VMRGSOGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvld mrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllmtlrl 5 ws Beta chain: TRBV20-1 / TRBJ2-5 / TRBC1 MLLLLLLLGPGSGLGAWSOHPSWVICKSGTSVKIECRSLDFQATTMFWYROFPK 10 QSLMLMATSNEGSKATYEQGVEKDKFLINHASLTLSTLTVTSAHPEDSSFYICSAK RGDAFGETQYFGPGTRLLVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwvngkev hsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgftsv syqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 15  HA2-MJ14-DP162 MGTM Sequence: Alpha chain: TRAV8-2 / TRAJ42 / TRAC MLLLLVPVLEVIFTLGGTRAQSVTQLDSHVSVSEGTPVLLRCNYSSSYSPSLFWYV OHPNKGLQLLLKYTSAATLVKGINGFEAEFKKSETSFHLTKPSAHMSDAAEYFCV 20 VMRGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvld mrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllmtlrl ws Beta chain: 25 TRBV20-1 / TRBJ2-5 / TRBC1 MLLLLLLLGPGSGLGAWSOHPSWVICKSGTSVKIECRSLDFQATTMFWYROFPK QSLMLMATSNEGSKATYEQGVEKDKFLINHASLTLSTLTVTSAHPEDSSFYICSAK RGDAFGETQYFGPGTRLLVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwvngkev hsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcgftsv 30 syqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ14-DP317 sequence (same CDRs as “TCR-101”): Alpha chain: TRAV38-2DV8 / TRAJ11 / TRAC 35 MACPGFLWALVISTCLEFSMAOTVTQSOPEMSVOEAETVTLSCTYDTSESDYYLF WYKQPPSROMILVIRQEAYKQQNATENRFSVNFOKAAKSFSLKISDSQLGDAAMY FCAYRSERYSTLTFGKGTMLLVSPDiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdk tvldmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnll mtlrlws 40 Beta chain: TRBV30 / TRBJ2-3 / TRBC1 MLCSLLALLLGTFFGVRSOTIHOWPATLVOPVGSPLSLECTVEGTSNPNLYWYRQA AGRGLOLLFYSVGIGOISSEVPQNLSASRPODROFILSSKKLLLSDSGFYLCAWSVP 45 YLAGGKRPDTOYFGPGTRLTVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwvng kevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcg ftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ14-DP317 MGTM Sequence (also known as “TCR-101” and “MJ14-DP317”): 50 Alpha chain: 2023204645   13 Jul 2023 TRAV38-2DV8 / TRAJ11 / TRAC MACPGFLWALVISTCLEFSMAOTVTQSOPEMSVOEAETVTLSCTYDTSESDYYLF WYKOPPSROMILVIRQEAYKOONATENRFSVNFOKAAKSFSLKISDSOLGDAAMY FCAYRSERYSTLjTFGKGTMLLVSPDiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvyitdk 5 tvldmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnll mtlrlws Beta chain: TRBV30 / TRBJ2-3 / TRBC1 10 MLCSLLALLLGTFFGVRSQTIHQWPATLVQPVGSPLSLECTVEGTSNPNLYWYRQA AGRGLQLLFYSVGIGQISSEVPQNLSASRPQDRQFILSSKKLLLSDSGFYLCAWSVP YLAGGKRPDTOYFGPGTRLTVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwvng kevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgradcg ftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 15 HA2-MJ14-DP331 sequence: Alpha chain: TRAV36DV7 / TRAJ42 / TRAC MMKCPQALLAIFWLLLSWVSSEDKVVQSPLSLVVHEGDTVTLNCSYEVTNFRSLL 20 WYKQEKKAPTFLFMLTSSGIEKKSGRLSSILDKKELFSILNITATQTGDSAIYLCAV EAGYGGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdkt vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllm tlrlws 25 Beta chain: TRBV18 / TRB J1 -3 / TRBC1 MDTRLLCCAVICLLGAGLSNAGVMQNPRHLVRRRGQEARLRCSPMKGHSHVYW YROLPEEGLKFMVYLQKENIIDESGMPKERFSAEFPKEGPSILRIOOVVRGDSAAYF CASSPRTGRGGNTIYFGEGSWLTWEdlnkvfppevavfepseaeishtqkatlvclatgffbdhvelsw 30 wvngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawg radcgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ14-DP331 MGTM Sequence: Alpha chain: 35 TRAV36DV7 / TRAJ42 / TRAC MMKCPQALLAIFWLLLSWVSSEDKVVQSPLSLVVHEGDTVTLNCSYEVTNFRSLL WYKQEKKAPTFLFMLTSSGIEKKSGRLSSILDKKELFSILNITATQTGDSAIYLCAV EAGYGGSOGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdkt vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllm 40 tlrlws Beta chain: TRBV 18 / TRB J1 -3 / TRBC 1 MDTRLLCCAVICLLGAGLSNAGVMQNPRHLVRRRGQEARLRCSPMKGHSHVYW 45 YROLPEEGLKFMVYLQKENIIDESGMPKERFSAEFPKEGPSILRIOOVVRGDSAAYF CASSPRTGRGGNTIYFGEGSWLTWEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelsw wvngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawg radcgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 50 HA2-MJ2-DP22 sequence: 2023204645   13 Jul 2023 Alpha chain: TRAV35 / TRAJ42 / TRAC MLLEHLLIILWMQLTWVSGQQLNQSPQSMFIQEGEDVSMNCTSSSIFNTWLWYKQ EPGEGPVLLIALYKAGELTSNGRLTAQFGITRKDSFLNISASIPSDVGIYFCAGPFGY 5 GGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdktvldmrs mdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllmtlrlws Beta chain: TRBV7-8 / TRBJ1 -2 / TRBC1 10 MGTRLLCWVVLGFLGTDHTGAGVSQSPRYKVAKRGQDVALRCDPISGHVSLFWY OOALGOGPEFLTYFQNEAQLDKSGLPSDRFFAERPEGSVSTLKIQRTOOEDSAVYL CASSLIGRGWDGYTFGSGTRLTVVEdlnkvfppevavfepseaeishtqkatlvclatgfipdhvelsww vngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgra dcgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 15 HA2-MJ2-DP22 MGTM Sequence: Alpha chain: TRAV35 / TRAJ42 / TRAC MLLEHLLIILWMQLTWVSGQQLNQSPQSMFIQEGEDVSMNCTSSSIFNTWLWYKQ 20 EPGEGPVLLIALYKAGELTSNGRLTAQFGITRKDSFLNISASIPSDVGIYFCAGPFGY GGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvyitdktvldmrs mdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllmtlrlws Beta chain: 25 TRBV7-8 / TRBJ1-2 / TRBC 1 MGTRLLCWVVLGFLGTDHTGAGVSOSPRYKVAKRGODVALRCDPISGHVSLFWY OQALGOGPEFLTYFQNEAQLDKSGLPSDRFFAERPEGSVSTLKIQRTOQEDSAVYL CASSLIGRGWDGYTFGSGTRLTVVEdlnkvfppevavfepseaeishtqkatlvclatgffbdhvelsww vngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgra 30 dcgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ2-DP24 sequence: Alpha chain: TRAV8-2 / TRAJ13 / TRAC 35 MLLLLVPVLEVIFTLGGTRAOSVTQLDSHVSVSEGTPVLLRCNYSSSYSPSLFWYV OHPNKGLQLLLKYTSAATLVKGINGFEAEFKKSETSFHLTKPSAHMSDAAEYFCV VTGGSGGYOKVTFGTGTKLOVIPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdkt vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllm tlrlws 40 Beta chain: TRBV7-9 / TRBJ2-5 / TRBC1 MGTSLLCWMALCLLGADHADTGVSODPRHKITKRGQNVTFRCDPISEHNRLYWY ROTLGOGPEFLTYFQNEAQLEKSRLLSDRFSAERPKGSFSTLEIQRTEOGDSAMYL 45 CASSPLGTDOETOYFGPGTRLLVLEdlnkvfppevavfepseaeishtqkatlvclatgffbdhvelswwv ngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgrad cgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ2-DP24 MGTM Sequence: 50 Alpha chain: 2023204645   13 Jul 2023 TRAV8-2 / TRAJ13 / TRAC MLLLLVPVLEVIFTLGGTRAOSVTQLDSHVSVSEGTPVLLRCNYSSSYSPSLFWYV OHPNKGLQLLLKYTSAATLVKGINGFEAEFKKSETSFHLTKPSAHMSDAAEYFCV VTGGSGGYQKVTFGTGTKLQVIPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvyitdkt 5 vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllm tlrlws Beta chain: TRBV7-9 / TRBJ2-5 / TRBC1 10 MGTSLLCWMALCLLGADHADTGVSQDPRHKITKRGQNVTFRCDPISEHNRLYWY ROTLGOGPEFLTYFQNEAQLEKSRLLSDRFSAERPKGSFSTLEIQRTEOGDSAMYL CASSPLGTDOETOYFGPGTRLLVLEdlnkvfppevavfepseaeishtqkatlvclatgffodhvelswwv ngkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgrad cgftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 15 HA2-MJ9-DP5 sequence: Alpha chain: TRAV21 / TRAJ42 / TRAC METLLGLLILWLQLQWVSSKQEVTQIPAALSVPEGENLVLNCSFTDSAIYNLQWFR 20 ODPGKGLTSLLLIQSSOREOTSGRLNASLDKSSGRSTLYIAASOPGDSATYLCAVR PKNYGGSQGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdkt vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpspesscdvklveksfetdtnlnfqnlsvigfrilllkvagfnllm tlrlws 25 Beta chain: TRBV18 / TRBJ2- 1 / TRBC1 MDTRLLCCAVICLLGAGLSNAGVMQNPRHLVRRRGQEARLRCSPMKGHSHVYW YROLPEEGLKFMVYLQKENIIDESGMPKERFSAEFPKEGPSILRIOOVVRGDSAAYF CASSLTSGSSNEQFFGPGTRLTVLEdlnkvfppevavfepseaeishtqkatlvclatgffbdhvelswwvn 30 gkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnpmhfrcqvqfyglsendewtqdrakpvtqivsaeawgradc gftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf HA2-MJ9-DP5 MGTM Sequence: Alpha chain: 35 TRAV21 / TRAJ42 / TRAC METLLGLLILWLQLQWVSSKQEVTQIPAALSVPEGENLVLNCSFTDSAIYNLQWFR ODPGKGLTSLLLIQSSOREOTSGRLNASLDKSSGRSTLYIAASOPGDSATYLCAVR PKNYGGSOGNLIFGKGTKLSVKPNiqnpdpavyqlrdskssdksvclftdfdsqtnvsqskdsdvvitdkt vldmrsmdfksnsavawsnksdfacanafnnsiipedtffpssdvpcdvklveksfetdtnlnfqnllvivlrilllkvagfnllm 40 tlrlws Beta chain: TRBV 18 / TRBJ2- 1 / TRBC 1 MDTRLLCCAVICLLGAGLSNAGVMQNPRHLVRRRGQEARLRCSPMKGHSHVYW 45 YROLPEEGLKFMVYLQKENIIDESGMPKERFSAEFPKEGPSILRIOOVVRGDSAAYF CASSLTSGSSNEQFFGPGTRLTVLEdlnkvfppevavfepseaeishtqkatlvclatgffpdhvelswwvn gkevhsgvstdpqplkeqpalndsryclssrlrvsatfwqnprnhfrcqvqfyglsendewtqdrakpvtqivsaeawgradc gftsvsyqqgvlsatilyeillgkatlyavlvsalvlmamvkrkdf 2023204645   13 Jul 2023 * Table 1 providing representative TCR sequences are grouped according to MHC serotype presentation and sub-grouped according to different peptides presented by the MHC serotype and bound by the sub-grouped TCRs. Individual TCRs, such as those representatively exemplified in the tables, are described and claimed, as well as the genus 5 of binding proteins that bind a peptide epitope sequence described herein either alone or in a complex with an MHC, such as those grouped in the tables provided herein. In addition, TRAV, TRAJ, and TRAC genes for each TCR alpha chain described herein, and TRBV, TRBJ, and TRBC genes for each TCR beta chain described herein, are provided. Sequences for each TCR described herein are provided as pairs of cognate alpha chain and 10 beta chains for each named TCR. TCR sequences described herein are annotated. Variable domain sequences are capitalized. Constant domain sequences are in lower case. CDR1, CDR2, and CDR3 sequences are annotated using bold and underlined text. CDR1, CDR2, and CDR3 are shown in standard order of appearance from left (N-terminus) to right (C-terminus). TRAV, TRAJ, and TRAC genes for each TCR alpha chain described herein, and 15 TRBV, TRBJ, and TRBC genes for each TCR beta chain described herein, are annotated according to well-known IMGT nomenclature described herein. The designation “DP” in a clone name identifies a TCR that recognizes both SNP peptide-loaded and REF peptide-loaded MHC dextramers. The designation “SP” in a clone name identifies a TCR that only recognizes REF peptide-loaded MHC dextramers 20 Table 2 Vector: pTSLV101-MSCV-MGTMA-QQ-CD8 tggaagggctaattcactcccaaagaagacaagatatccttgatctgtggatctaccacacacaaggctacttccctgattagcagaa ctacacaccagggccaggggtcagatatccactgacctttggatggtgctacaagctagtaccagttgagccagataaggtagaag 25 aggccaataaaggagagaacaccagcttgttacaccctgtgagcctgcatgggatggatgacccggagagagaagtgttagagtg gaggtttgacagccgcctagcatttcatcacgtggcccgagagctgcatccggagtacttcaagaactgctgatatcgagcttgctac aagggactttccgctggggactttccagggaggcgtggcctgggcgggactggggagtggcgagccctcagatcctgcatataa gcagctgctttttgcctgtactgggtctctctggttagaccagatctgagcctgggagctctctggctaactagggaacccactgctta agcctcaataaagcttgccttgagtgcttcaagtagtgtgtgcccgtctgttgtgtgactctggtaactagagatccctcagaccctttta 30 gtcagtgtggaaaatctctagcagtggcgcccgaacagggacttgaaagcgaaagggaaaccagaggagctctctcgacgcagg actcggcttgctgaagcgcgcacggcaagaggcgaggggcggcgactggtgagtacgccaaaaattttgactagcggaggcta gaaggagagagatgggtgcgagagcgtcagtattaagcgggggagaattagatcgcgatgggaaaaaattcggttaaggccagg gggaaagaaaaaatataaattaaaacatatagtatgggcaagcagggagctagaacgattcgcagttaatcctggcctgttagaaac atcagaaggctgtagacaaatactgggacagctacaaccatcccttcagacaggatcagaagaacttagatcattatataatacagta 35 gcaaccctctattgtgtgcatcaaaggatagagataaaagacaccaaggaagctttagacaagatagaggaagagcaaaacaaaa gtaagaccaccgcacagcaagcggccggccgctgatcttcagacctggaggaggagatatgagggacaattggagaagtgaatt atataaatataaagtagtaaaaattgaaccattaggagtagcacccaccaaggcaaagagaagagtggtgcagagagaaaaaaga gcagtgggaataggagctttgttccttgggttcttgggagcagcaggaagcactatgggcgcagcgtcaatgacgctgacggtaca ggccagacaattattgtctggtatagtgcagcagcagaacaatttgctgagggctattgaggcgcaacagcatctgttgcaactcaca 2023204645   13 Jul 2023 gtctggggcatcaagcagctccaggcaagaatcctggctgtggaaagatacctaaaggatcaacagctcctggggatttggggttg ctctggaaaactcatttgcaccactgctgtgccttggaatgctagttggagtaataaatctctggaacagatttggaatcacacgacct ggatggagtgggacagagaaattaacaattacacaagcttaatacactccttaattgaagaatcgcaaaaccagcaagaaaagaat gaacaagaattattggaattagataaatgggcaagtttgtggaattggtttaacataacaaattggctgtggtatataaaattattcataat 5 gatagtaggaggcttggtaggtttaagaatagtttttgctgtactttctatagtgaatagagttaggcagggatattcaccattatcgtttc agacccacctcccaaccccgaggggacccgacaggcccgaaggaatagaagaagaaggtggagagagagacagagacagat ccattcgattagtgaacggatctcgacggtatcgccgaattaattcacaaatggcagtattcatccacaattttaaaagaaaaggggg gattggggggtacagtgcaggggaaagaatagtagacataatagcaacagacatacaaactaaagaattacaaaaacaaattaca aaaattcaaaattttcgggtttattacaggCGcGCcagagatccagtttggacCTgcAGGTGAAAGACCCCAC 10 CTGTAGGTTTGGCAAGtTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAA AATACATAACTGAGAATAGAGAAGTTCAGATCAAGGTTAGGAACAGAGAG ACAGCAGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCC CGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCCGCCCTCAGC AGTTTCTAGCGAACCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAAT 15 GACCCTGTGCCTTATTTGAACTAACCAATCAGTTtGCTTCTtGCTTCTGTTtGt GtGCTTCTGCTCCCtGAGCTCAATAAAAGAGCCCACAACCCCTCACTtGGtGg GCCAGTCCTCtGATAGACTGtGTCcCCtGGaTACCCGTATggtaccgctagcgccaccATGtac atccagaaccccgaccccgccgtgtaccagctgagagacagcaagtccagcgacaagagcgtgtgtctgttTacGgacttc gacagccagaccaacgtgAGTcaAagcaaggacagcgacgtCtacatAacGgataagACcgtgctggacatgcgga 20 gcatggacttcaagagcaacagcgccgtggcctggtccaacaagagcgacttcgcctgcgccaacgccttcaacaacagcat catccccgaggacacctttttccccagcAGCGACGTGCCctgcgacgtgaaactggtggagaagtccttcgagacag acaccaatctgaactttcagaacctgCTGgtgatcgTGCTGcggatcctgctgctgaaagtggccggcttcaatctgctga Z‘g«cccZ‘gcggcZ‘gZ‘gg«gc«gcAGAGCCAAAAGAAGCGGGAGCGGTgccaccaatttttccctgctgaa gcaggccggcgatgtggaggagaatcctggcccCATGGCGCTGCCGGTGACTGCTCTGCTGCTGC 25 CCCTGGCGCTGCTGCTGCACGCCGCACGTCCGGAGCTGCCTACCCAGGGCAC CTTCTCTAACGTGTCGACCAACGTGAGCAGCGGATCTGGCTCCGGAG4GC7T CCCA CCCA GGGTA CTTTCTCGAA CGTGTCCA CAAA CGTGTCCTCCCA GTTTCGGGTG A GTCCCCTGGA CCGCA CCTGGAA CCTGGGGGA GA CCGTGGA GCTCAAA TGTCA GGT CCTCTTGTCGAA TCCAA CCA GCGGGTGCA GTTGGCTA TTCCA GCCGCGCGGTGCGG 30 CGGCTTCCCCAA CCTTCCTGCTTTA CCTGTCTCA GAA CAA GCCCAA GGCCGCCGA GG GCCTCGA CA CCCA GCGTTTCTCCGGCAA GCGCCTGGGCGA CA CCTTCGTCCTGA CC CTGA GTGA CTTCA GAA GGGA GAA CGAGGGCTA CT A CTTCTGTTCCGCGCTCA GCAA C A GCA TCA TGTA TTTCA GTCA CTTTGTCCCCGTGTTCCTCCCTGCAAAA CCTA CGA CCA CA CCTGCTCCCA GGCCCCCGA CTCCGGCGCCAA CCA TCGCCTCA CA GCCGCTTTCC 35 CTGCGCCCCGAGGCCTGCCGACCGGCAGCCGGCGGCGCCGTGCACACCCGCGGC CTTGA TTTCGCTTGTGA CA TCTA TA TTTGGGCTCCCCTGGCGGGCA CCTGCGGGGTG CTGCTGCTGTCTCTGGTGA TCA CTCTGTA CTGCAA CCA CCGCAA CCGCCGCA GA GTC TGTA A GTGCCCA CGGCCCGTGGTGAA GTCCGGGGA CAA GCCCTCTCTGTCCGCCCG CZ4CGTGCGCGCCAAGCGCAGCGGCTCCGGTGCCACCAACTTTTCTCTCCTGAA 40 GCAGGCCGGTGATGTGGAGGAGAATCCAGGACCGATGCGTCCTCGCCTTTGGC TACTGCTGGCAGCGCAGCTGACCGTCCTACATGGCAACTCCGTGCTGCAGCAGA CGCCTGCCTACATCAAGGTGCAGACTAACAAGATGGTGATGCTGTCATGCGAG GCTAAGATAAGCCTGTCCAACATGCGCATCTATTGGCTCCGCCAGCGACAGGCC CCGAGCTCCGACAGCCACCACGAGTTCCTGGCCCTTTGGGATTCCGCCAAAGGT 45 ACTATCCATGGAGAAGAGGTGGAACAGGAGAAGATCGCGGTGTTCCGCGACGC CTCCAGGTTTATTCTCAACCTGACCAGTGTCAAGCCTGAAGATTCTGGCATCTA CTTCTGTATGATCGTGGGCTCCCCGGAGCTGACCTTCGGCAAAGGCACTCAGCT TTCTGTGGTCGACTTTCTCCCTACCACCGCTCAGCCAACCAAGAAATCCACCCT GAAGAAGCGGGTATGCCGACTGCCCCGCCCTGAGACTCAGAAGGGCCCTCTGT 50 GCTCTCCCATCACCCTTGGTTTGCTGGTTGCCGGCGTCCTGGTGCTGTTGGTGTC 2023204645   13 Jul 2023 CTTAGGTGTCGCCATCCACCTGTGCTGCCGCCGGCGTAGAGCCCGCCTCCGTTT TATGAAGCAGTTCTACAAGTGATAAatcgatagatcctaatcaacctctggattacaaaatttgtgaaagattg actggtattcttaactatgttgctccttttacgctatgtggatacgctgctttaatgcctttgtatcatgctattgcttcccgtatggctttcattt tctcctccttgtataaatcctggttgctgtctctttatgaggagttgtggcccgttgtcaggcaacgtggcgtggtgtgcactgtgtttgct 5 gacgcaacccccactggttggggcattgccaccacctgtcagctcctttccgggactttcgctttccccctccctattgccacggcgg aactcatcgccgcctgccttgcccgctgctggacaggggctcggctgttgggcactgacaattccgtggtgttgtcggggaaatcat cgtcctttccttggctgctcgcctgtgttgccacctggattctgcgcgggacgtccttctgctacgtcccttcggccctcaatccagcg gaccttccttcccgcggcctgctgccggctctgcggcctcttccgcgtcttcgccttcgccctcagacgagtcggatctccctttggg ccgcctccccgcctgagatcctttaagaccaatgacttacaaggcagctgtagatcttagccactttttaaaagaaaaggggggactg 10 gaagggctaattcactcccaacgaagacaagatctgctttttgcttgtactgggtctctctggttagaccagatctgagcctgggagct ctctggctaactagggaacccactgcttaagcctcaataaagcttgccttgagtgcttcaagtagtgtgtgcccgtctgttgtgtgactc tggtaactagagatccctcagacccttttagtcagtgtggaaaatctctagcagtagtagttcatgtcatcttattattcagtatttataactt gcaaagaaatgaatatcagagagtgagaggcccgggttaattaaggaaagggctagatcattcttgaagacgaaagggcctcgtg atacgcctatttttataggttaatgtcatgataataatggtttcttagacgtcaggtggcacttttcggggaaatgtgcgcggaaccccta 15 tttgtttatttttctaaatacattcaaatatgtatccgctcatgagacaataaccctgataaatgcttcaataatattgaaaaaggaagagta tgagtattcaacatttccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctcacccagaaacgctggtgaaagtaaa agatgctgaagatcagttgggtgcacgagtgggttacatcgaactggatctcaacagcggtaagatccttgagagttttcgccccga agaacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcccgtgttgacgccgggcaagagcaactcggtc gccgcatacactattctcagaatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatgacagtaagagaatt 20 atgcagtgctgccataaccatgagtgataacactgcggccaacttacttctgacaacgatcggaggaccgaaggagctaaccgcttt tttgcacaacatgggggatcatgtaactcgccttgatcgttgggaaccggagctgaatgaagccataccaaacgacgagcgtgaca ccacgatgcctgtagcaatggcaacaacgttgcgcaaactattaactggcgaactacttactctagcttcccggcaacaattaataga ctggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccggctggctggtttattgctgataaatctggagccggt gagcgtgggtctcgcggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacacgacggggagtca 25 ggcaactatggatgaacgaaatagacagatcgctgagataggtgcctcactgattaagcattggtaactgtcagaccaagtttactca tatatactttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcctttttgataatctcatgaccaaaatcccttaacg tgagttttcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctgcttgc aaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcag agcgcagataccaaatactgttcttctagtgtagccgtagttaggccaccacttcaagaactctgtagcaccgcctacatacctcgctc 30 tgctaatcctgttaccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggc gcagcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatacctacagc gtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggaga gcgcacgagggagcttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgt gatgctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctggccttttgctca 35 catgttctttcctgcgttatccCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCT GATACCGCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGA AGCGGAAGAGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTC ATTAATGCAGCAAGCTCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGA GGCCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGG 40 CCTAGGCTTTTGCAAAAAGCTCCCCGTGGCACGACAGGTTTCCCGACTGGAAAG CGGGCAGTGAGCGCAACGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCC CAGGCTTTACACTTTATGCTTCCGGCTCGTATGTTGTGTGGAATTGTGAGCGGA TAACAATTTCACACAGGAAACAGCTATGACATGATTACGAATTTCACAAATAA AGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCT 45 TATCATGTCTGGATCAACTGGATAACTCAAGCTAACCAAAATCATCCCAAACTT CCCACCCCATACCCTATTACCACTGCCAATTACCTGTGGTTTCATTTACTCTAAA CCTGTGATTCCTCTGAATTATTTTCATTTTAAAGAAATTGTATTTGTTAAATATG TACTACAAACTtagtagt 2023204645   13 Jul 2023 * MSCV promoter is in bold. MGTM-alpha is annotated using bold and italic text. Q-tag 1 is annotated using bold and underlined text. Q-tag 2 is annotated using italic and underlined text. CD8-alpha is in italic. CD8-beta is underlined. 5 Vector: pTSLV102-MSCV-MGTM-Q-CD8 tggaagggctaattcactcccaaagaagacaagatatccttgatctgtggatctaccacacacaaggctacttccctgattagcagaa ctacacaccagggccaggggtcagatatccactgacctttggatggtgctacaagctagtaccagttgagccagataaggtagaag aggccaataaaggagagaacaccagcttgttacaccctgtgagcctgcatgggatggatgacccggagagagaagtgttagagtg gaggtttgacagccgcctagcatttcatcacgtggcccgagagctgcatccggagtacttcaagaactgctgatatcgagcttgctac 10 aagggactttccgctggggactttccagggaggcgtggcctgggcgggactggggagtggcgagccctcagatcctgcatataa gcagctgctttttgcctgtactgggtctctctggttagaccagatctgagcctgggagctctctggctaactagggaacccactgctta agcctcaataaagcttgccttgagtgcttcaagtagtgtgtgcccgtctgttgtgtgactctggtaactagagatccctcagaccctttta gtcagtgtggaaaatctctagcagtggcgcccgaacagggacttgaaagcgaaagggaaaccagaggagctctctcgacgcagg actcggcttgctgaagcgcgcacggcaagaggcgaggggcggcgactggtgagtacgccaaaaattttgactagcggaggcta 15 gaaggagagagatgggtgcgagagcgtcagtattaagcgggggagaattagatcgcgatgggaaaaaattcggttaaggccagg gggaaagaaaaaatataaattaaaacatatagtatgggcaagcagggagctagaacgattcgcagttaatcctggcctgttagaaac atcagaaggctgtagacaaatactgggacagctacaaccatcccttcagacaggatcagaagaacttagatcattatataatacagta gcaaccctctattgtgtgcatcaaaggatagagataaaagacaccaaggaagctttagacaagatagaggaagagcaaaacaaaa gtaagaccaccgcacagcaagcggccggccgctgatcttcagacctggaggaggagatatgagggacaattggagaagtgaatt 20 atataaatataaagtagtaaaaattgaaccattaggagtagcacccaccaaggcaaagagaagagtggtgcagagagaaaaaaga gcagtgggaataggagctttgttccttgggttcttgggagcagcaggaagcactatgggcgcagcgtcaatgacgctgacggtaca ggccagacaattattgtctggtatagtgcagcagcagaacaatttgctgagggctattgaggcgcaacagcatctgttgcaactcaca gtctggggcatcaagcagctccaggcaagaatcctggctgtggaaagatacctaaaggatcaacagctcctggggatttggggttg ctctggaaaactcatttgcaccactgctgtgccttggaatgctagttggagtaataaatctctggaacagatttggaatcacacgacct 25 ggatggagtgggacagagaaattaacaattacacaagcttaatacactccttaattgaagaatcgcaaaaccagcaagaaaagaat gaacaagaattattggaattagataaatgggcaagtttgtggaattggtttaacataacaaattggctgtggtatataaaattattcataat gatagtaggaggcttggtaggtttaagaatagtttttgctgtactttctatagtgaatagagttaggcagggatattcaccattatcgtttc agacccacctcccaaccccgaggggacccgacaggcccgaaggaatagaagaagaaggtggagagagagacagagacagat ccattcgattagtgaacggatctcgacggtatcgccgaattaattcacaaatggcagtattcatccacaattttaaaagaaaaggggg 30 gattggggggtacagtgcaggggaaagaatagtagacataatagcaacagacatacaaactaaagaattacaaaaacaaattaca aaaattcaaaattttcgggtttattacaggCGcGCcagagatccagtttggacCTgcAGGTGAAAGACCCCAC CTGTAGGTTTGGCAAGtTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAA AATACATAACTGAGAATAGAGAAGTTCAGATCAAGGTTAGGAACAGAGAG ACAGCAGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCC 35 CGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCCGCCCTCAGC AGTTTCTAGCGAACCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAAT GACCCTGTGCCTTATTTGAACTAACCAATCAGTTtGCTTCTtGCTTCTGTTtGt GtGCTTCTGCTCCCtGAGCTCAATAAAAGAGCCCACAACCCCTCACTtGGtGg GCCAGTCCTCtGATAGACTGtGTCcCCtGGaTACCCGTAcggtaccgctagcgccaccATGtac 40  1 Cl TCCA GAA CCCCGA CCCCGCCGTGTA CCA GCTGA GGGA CTCCAA GTCCA GCG A CAA GA GCGTGTGTCTGTTTA CGGA CTTCGA CA GCCA GA CCAA CGTGA GTCAAA G CAA GGA CA GCGA CGTCTA CA TAA CGGA TAA GA CCGTGCTGGA CA TGCGGA GCA T GGA CTTCAA GA GCAA CA GCGCCGTGGCCTGGTCCAA CAA GA GCGA CTTCGCCTG CGCCAA CGCCTTCAA CAA CA GCA TCA TCCCCGA GGA CA CCTTCTTCCCCA GCA GC 45  GA CGTGCCCTGCGA CGTGAAA CTGGTGGA GAA GTCCTTCGA GA CA GA CA CCAA T CTGAA CTTTCA GAA CCTGCTGGTGA TCGTGCTGCGGA TTCTGCTGCTGAAA GTGG CCGGCTTCAA TCTGCTGA TGA CCCTGCGGCTGTGGA GCA GCAGGGCT AAGAGGT CCGGCAGCGGAGCCACCAATTTTTCCCTGCTGAAACAGGCTGGTGACGTGGAA 2023204645   13 Jul 2023 GAAAACCCTGGCCCCATGGCGCTGCCCGTCACCGCGCTGCTGCTGCCCCTGGCG CTGCTGTTACACGCCGCTCGGCCAGAGCTTCCCACCCAGGGCACATTCTCCA ACGTGTCCACCAATGTGTCGGG4 GGCGGCGGA TCGTCCCA GTTCA GA GTGTCCC CTCTGGA CCGCA CCTGGAA CCTGGGCGA GA CCGTGGA GCTGAAA TGTCA GGTCCTG 5  CTGA GCAA CCCGA CCTCCGGGTGCAGTTGGCTGTTCCA GCCGCGTGGTGCTGCCGC AAGCCCTA CGTTCCTGCTTTA CCTGA GCCA GAA CAA GCCCAA GGCGGCGGA GGGCC TGGA CA CCCA GA GA TTCTCCGGCAA GCGCCTGGGGGA CA CA TTCGTGCTTA CTTTGA GCGA TTTCCGCA GA GA GAA CGA GGGCTA CT A TTTCTGTTCGGCGCTGA GCAA TTCCA TCA TGTA TTTCA GCCA CTTTGTGCCA GTGTTCCTGCCTGCCAA GCCTA CCA CAA CA CC 10  A GCTCCCCGTCCCCCGA CTCCGGCGCCTA CCA TCGCGA GTCAA CCGTTGA GCCTGA GGCCTGA GGCTTGTCGGCCCGCTGCGGGGGGTGCCGTCCA CA CCA GGGGCCTCGA CTTTGCGTGCGA CA TCTA TA TTTGGGCGCCTCTGGCGGGTA CCTGCGGGGTGCTGC TGCTGTCA TTGGTGA TTA CCCTGTA CTGCAA TCA CCGCAA CCGCCGGCGGGTCTGTA A GTGCCCA CGGCCTGTGGTCAA GTCCGGTGA CAAA CCGTCGCTCTCGGCTCGCTA C 15 GTGCGCGCTAAGCGCAGCGGTTCCGGGGCCACCAACTTTTCATTGCTGAAGCAG GCCGGTGATGTGGAGGAGAATCCAGGGCCCATGCGCCCCAGGCTTTGGCTCCTT CTTGCTGCTCAGCTCACTGTCTTGCATGGCAACTCCGTTCTGCAGCAGACTCCC GCCTACATCAAGGTGCAGACGAACAAGATGGTGATGCTGTCATGCGAGGCCAA GATCTCTCTTTCAAATATGAGAATTTATTGGCTACGACAGCGCCAGGCCCCCTC 20 CAGCGACAGCCACCACGAGTTCCTGGCGCTTTGGGATTCTGCTAAAGGCACCAT CCATGGAGAGGAGGTGGAACAGGAGAAGATAGCTGTCTTCCGCGACGCATCCC GCTTCATCCTGAACCTGACCAGCGTGAAGCCGGAGGACAGCGGCATCTACTTCT GTATGATCGTTGGCTCCCCCGAGCTGACCTTCGGCAAAGGCACCCAGCTGTCCG TGGTGGACTTCCTGCCCACCACAGCCCAGCCAACCAAGAAATCCACCCTCAAG 25 AAGCGCGTGTGCCGACTGCCCCGCCCTGAAACCCAGAAGGGCCCTCTGTGCTCC CCCATCACCCTTGGACTGCTGGTGGCGGGAGTCCTGGTGCTGCTCGTATCTCTG GGTGTCGCCATCCACCTGTGCTGCCGCCGCCGCCGCGCCCGCCTGAGGTTTATG AAACAGTTTTACAAGTGATAAatcgatagatcctaatcaacctctggattacaaaatttgtgaaagattgactggt attcttaactatgttgctccttttacgctatgtggatacgctgctttaatgcctttgtatcatgctattgcttcccgtatggctttcattttctcct 30 ccttgtataaatcctggttgctgtctctttatgaggagttgtggcccgttgtcaggcaacgtggcgtggtgtgcactgtgtttgctgacgc aacccccactggttggggcattgccaccacctgtcagctcctttccgggactttcgctttccccctccctattgccacggcggaactca tcgccgcctgccttgcccgctgctggacaggggctcggctgttgggcactgacaattccgtggtgttgtcggggaaatcatcgtcctt tccttggctgctcgcctgtgttgccacctggattctgcgcgggacgtccttctgctacgtcccttcggccctcaatccagcggaccttc cttcccgcggcctgctgccggctctgcggcctcttccgcgtcttcgccttcgccctcagacgagtcggatctccctttgggccgcctc 35 cccgcctgagatcctttaagaccaatgacttacaaggcagctgtagatcttagccactttttaaaagaaaaggggggactggaaggg ctaattcactcccaacgaagacaagatctgctttttgcttgtactgggtctctctggttagaccagatctgagcctgggagctctctggc taactagggaacccactgcttaagcctcaataaagcttgccttgagtgcttcaagtagtgtgtgcccgtctgttgtgtgactctggtaac tagagatccctcagacccttttagtcagtgtggaaaatctctagcagtagtagttcatgtcatcttattattcagtatttataacttgcaaag aaatgaatatcagagagtgagaggcccgggttaattaaggaaagggctagatcattcttgaagacgaaagggcctcgtgatacgcc 40 tatttttataggttaatgtcatgataataatggtttcttagacgtcaggtggcacttttcggggaaatgtgcgcggaacccctatttgtttatt tttctaaatacattcaaatatgtatccgctcatgagacaataaccctgataaatgcttcaataatattgaaaaaggaagagtatgagtatt caacatttccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctcacccagaaacgctggtgaaagtaaaagatgct gaagatcagttgggtgcacgagtgggttacatcgaactggatctcaacagcggtaagatccttgagagttttcgccccgaagaacgt tttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcccgtgttgacgccgggcaagagcaactcggtcgccgcat 45 acactattctcagaatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatgacagtaagagaattatgcagt gctgccataaccatgagtgataacactgcggccaacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcac aacatgggggatcatgtaactcgccttgatcgttgggaaccggagctgaatgaagccataccaaacgacgagcgtgacaccacga tgcctgtagcaatggcaacaacgttgcgcaaactattaactggcgaactacttactctagcttcccggcaacaattaatagactggatg gaggcggataaagttgcaggaccacttctgcgctcggcccttccggctggctggtttattgctgataaatctggagccggtgagcgt 50 gggtctcgcggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacacgacggggagtcaggcaac 2023204645   13 Jul 2023 tatggatgaacgaaatagacagatcgctgagataggtgcctcactgattaagcattggtaactgtcagaccaagtttactcatatatact ttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcctttttgataatctcatgaccaaaatcccttaacgtgagtttt cgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctgcttgcaaacaa aaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcagagcgc 5 agataccaaatactgttcttctagtgtagccgtagttaggccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaa tcctgttaccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagc ggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagc tatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgcac gagggagcttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctc 10 gtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctggccttttgctcacatgttct ttcctgcgttatccCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATA CCGCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGC GGAAGAGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTA ATGCAGCAAGCTCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCC 15 GCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTA GGCTTTTGCAAAAAGCTCCCCGTGGCACGACAGGTTTCCCGACTGGAAAGCGG GCAGTGAGCGCAACGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAG GCTTTACACTTTATGCTTCCGGCTCGTATGTTGTGTGGAATTGTGAGCGGATAA CAATTTCACACAGGAAACAGCTATGACATGATTACGAATTTCACAAATAAAGC 20 ATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTAT CATGTCTGGATCAACTGGATAACTCAAGCTAACCAAAATCATCCCAAACTTCCC ACCCCATACCCTATTACCACTGCCAATTACCTGTGGTTTCATTTACTCTAAACCT GTGATTCCTCTGAATTATTTTCATTTTAAAGAAATTGTATTTGTTAAATATGTAC T AC AAACT tagtagt 25 * MSCV promoter is in bold. Alpha chain constant domain is annotated using bold and italic text. Q-tag is annotated using bold and underlined text. CD8-alpha is in italic. CD8-beta is underlined. 30 Vector: TSC-101 npDNA Transposon: AATTAATTGCTTGCAATTAACCCTTTAACGGTTATAAGGATCTAGATGAGATAGAAAGA TTTGGTTTTCGGATTTGTGTTACATAAGATGCCTAAAATAAAAATTGAGATTCAATTTTT TTTAAACTTTTTTTTAATTGGTGGTAAGAATATTCCCTCTACCTGTTTGAGAGTAATGAA ATTGTAGTATGATTTTTCAACAAACTAAAAAAACAACATAAATCTCACATAATAACTTT 35 ATTTCAATCACACAATTGAATACCAATATTAATTAATGGTTGACAGTACTTACCAGCCT GCAGGTGAAAGACCCCACCTGTAGGTTTGGCAAGTTAGCTTAAGTAACGCCATTTTGCA AGGCATGGAAAATACATAACTGAGAATAGAGAAGTTCAGATCAAGGTTAGGAACAGA GAGACAGCAGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCT CAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCCGCCCTCAGCAGTTTCTAGCGAA 40 CCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAAC TAACCAATCAGTTTGCTTCTTGCTTCTGTTTGTGTGCTTCTGCTCCCTGAGCTCAATAAA AGAGCCCACAACCCCTCACTTGGTGGGCCAGTCCTCTGATAGACTGTGTCCCCTGGATA 2023204645   13 Jul 2023 CCCGTACGGTACCGCTAGCGCCACCATGCTGTGTAGCCTGCTGGCCCTGCTCCTGGGCA CATTTTTTGGCGTCAGATCCCAGACCATCCATCAGTGGCCTGCCACACTGGTGCAGCCT GTTGGATCTCCCCTGTCTCTGGAATGTACCGTGGAAGGCACAAGCAACCCCAACCTCTA CTGGTATAGGCAGGCCGCTGGAAGAGGACTGCAGCTGCTGTTTTACAGCGTCGGCATC 5 GGCCAGATCAGCAGCGAGGTTCCACAGAATCTGAGCGCCTCCAGGCCTCAGGACAGAC AGTTTATCCTGAGCAGCAAGAAGCTGCTGCTGAGCGACTCCGGCTTTTACCTCTGTGCT TGGAGCGTTCCATACCTGGCCGGTGGCAAACGCCCTGACACTCAATATTTCGGCCCAGG CACCCGGCTGACAGTGCTCGAAGATCTGAACAAGGTGTTCCCTCCAGAGGTGGCCGTG TTCGAGCCTTCTAAGGCCGAGATCGCCCACACACAAAAAGCCACCCTCGTGTGCCTGG 10 CCACCGGCTTTTTCCCCGACCACGTGGAACTGTCTTGGTGGGTCAACGGCAAAGAGGTG CACTCCGGCGTGTCAACGGATCCCCAGCCTCTGAAAGAACAGCCTGCCCTGAACGACA GCCGGTACTGCCTGAGCTCCAGACTGAGAGTGTCCGCCACCTTCTGGCAGAACCCCCG GAACCACTTCAGATGCCAGGTGCAGTTTTACGGCCTGAGCGAGAACGACGAGTGGACC CAGGACAGAGCCAAGCCCGTGACACAAATCGTGTCTGCCGAAGCCTGGGGAAGAGCC 15 GATTGCGGCATCACCAGCGCCTCCTATCACCAGGGCGTGCTGAGCGCCACAATCCTGTA CGAAATCCTGCTGGGCAAGGCCACCCTGTACGCCGTGCTGGTGTCTGCTCTGGTGCTGA TGGCCATGGTCAAGCGGAAGGACTTTGGCAGCGGCAGAGCCAAAAGGTCCGGGAGCG GTGCGACAAACTTTAGCCTGTTGAAACAAGCCGGCGACGTTGAAGAGAACCCCGGACC TATGGCCTGTCCTGGCTTCCTGTGGGCCCTTGTGATCAGCACTTGCCTGGAATTCAGCA 20 TGGCTCAGACAGTCACCCAGTCTCAGCCCGAAATGAGCGTCCAAGAGGCTGAAACCGT GACTCTGTCTTGTACCTACGACACCTCCGAGAGCGATTACTACCTCTTTTGGTATAAGC AACCGCCGTCCAGGCAAATGATCCTCGTGATCCGGCAAGAAGCTTACAAACAGCAGAA TGCTACCGAAAACCGGTTCTCCGTCAATTTTCAGAAAGCCGCTAAGAGCTTTAGCCTGA AAATCTCCGACTCTCAGCTCGGCGACGCTGCTATGTATTTCTGTGCCTACCGCAGTGAG 25 CGCTACAGCACTTTGACTTTCGGGAAGGGGACTATGCTTCTAGTCTCTCCAGACATCCA GAACCCCGACCCCGCCGTGTACCAGCTGAGGGACTCCAAGTCCAGCGACAAGAGCGTG TGTCTGTTTACGGACTTCGACAGCCAGACCAACGTGAGTCAAAGCAAGGACAGCGACG TCTACATAACGGATAAGACCGTGCTGGACATGCGGAGCATGGACTTCAAGAGCAACAG CGCCGTGGCCTGGTCCAACAAGAGCGACTTCGCCTGCGCCAACGCCTTCAACAACAGC 30 ATCATCCCCGAGGACACCTTCTTCCCCAGCAGCGACGTGCCCTGCGACGTGAAACTGGT GGAGAAGTCCTTCGAGACAGACACCAATCTGAACTTTCAGAACCTGCTGGTGATCGTG CTGCGGATTCTGCTGCTGAAAGTGGCCGGCTTCAATCTGCTGATGACCCTGCGGCTGTG GAGCAGCAGGGCTAAGAGGTCCGGCAGCGGAGCCACCAATTTTTCCCTGCTGAAACAG GCTGGTGACGTGGAAGAAAACCCTGGCCCCATGGCGCTGCCCGTCACCGCGCTGCTGC 35 TGCCCCTGGCGCTGCTGTTACACGCCGCTCGGCCAGAGCTTCCCACCCAGGGCACATTC TCCAACGTGTCCACCAATGTGTCGGGAGGCGGCGGATCGTCCCAGTTCAGAGTGTCCCC 2023204645   13 Jul 2023 TCTGGACCGCACCTGGAACCTGGGCGAGACCGTGGAGCTGAAATGTCAGGTCCTGCTG AGCAACCCGACCTCCGGGTGCAGTTGGCTGTTCCAGCCGCGTGGTGCTGCCGCAAGCC CTACGTTCCTGCTTTACCTGAGCCAGAACAAGCCCAAGGCGGCCGAGGGCCTGGACAC CCAGAGATTCTCCGGCAAGCGCCTGGGGGACACATTCGTGCTTACTTTGAGCGATTTCC 5 GCAGAGAGAACGAGGGCTACTATTTCTGTTCGGCGCTGAGCAATTCCATCATGTATTTC AGCCACTTTGTGCCAGTGTTCCTGCCTGCCAAGCCTACCACAACACCAGCTCCCCGTCC CCCGACTCCGGCGCCTACCATCGCGAGTCAACCGTTGAGCCTGAGGCCTGAGGCTTGTC GGCCCGCTGCGGGGGGTGCCGTCCACACCAGGGGCCTCGACTTTGCGTGCGACATCTA TATTTGGGCGCCTCTGGCGGGTACCTGCGGGGTGCTGCTGCTGTCATTGGTGATTACCC 10 TGTACTGCAATCACCGCAACCGCCGGCGGGTCTGTAAGTGCCCACGGCCTGTGGTCAA GTCCGGTGACAAACCGTCGCTCTCGGCTCGCTACGTGCGCGCTAAGCGCAGCGGTTCCG GGGCCACCAACTTTTCATTGCTGAAGCAGGCCGGTGATGTGGAGGAGAATCCAGGGCC CATGCGCCCCAGGCTTTGGCTCCTTCTTGCTGCTCAGCTCACTGTCTTGCATGGCAACTC CGTTCTGCAGCAGACTCCCGCCTACATCAAGGTGCAGACGAACAAGATGGTGATGCTG 15 TCATGCGAGGCCAAGATCTCTCTTTCAAATATGAGAATTTATTGGCTACGACAGCGCCA GGCCCCCTCCAGCGACAGCCACCACGAGTTCCTGGCGCTTTGGGATTCTGCTAAAGGCA CCATCCATGGAGAGGAGGTGGAACAGGAGAAGATAGCTGTCTTCCGCGACGCATCCCG CTTCATCCTGAACCTGACCAGCGTGAAGCCGGAGGACAGCGGCATCTACTTCTGTATGA TCGTTGGCTCCCCCGAGCTGACCTTCGGCAAAGGCACCCAGCTGTCCGTGGTGGACTTC 20 CTGCCCACCACAGCCCAGCCAACCAAGAAATCCACCCTCAAGAAGCGCGTGTGCCGAC TGCCCCGCCCTGAAACCCAGAAGGGCCCTCTGTGCTCCCCCATCACCCTTGGACTGCTG GTGGCGGGAGTCCTGGTGCTGCTCGTATCTCTGGGTGTCGCCATCCACCTGTGCTGCCG CCGCCGCCGCGCCCGCCTGAGGTTTATGAAACAGTTTTACAAGTGATAAATCGATAGAT CCTAATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGTATTCTTAACTATGT 25 TGCTCCTTTTACGCTATGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTC CCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTCTCTTTATGAGGA GTTGTGGCCCGTTGTCAGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCC CCACTGGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACTTTCGCTTTCCCCC TCCCTATTGCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCT 30 CGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAATCATCGTCCTTTCCTTG GCTGCTCGCCTGTGTTGCCACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTTC GGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTGCGGCCTCTTC CGCGTCTTCGCCTTCGCCCTCAGACGAGTCGGATCTCCCTTTGGGCCGCCTCCCCGCCT GAGATCCTTTAAGACCAATGCTGGAGTTCTTCGCCCACCCCAACTTGTTTATTGCAGCT 35 TATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTC ACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGTATACA 2023204645   13 Jul 2023 GGTTACCTCAGTCTCCTAGGTACGTCTTATATCTATGAAAAAACATTCAAAAGCACAAC ATCTAGAAGAACTTACCTTTTTTCACCACTCTATTGCAAAGATATGTACCGATTTCTCTC GAAGTACAAAAAACCGCTAGTTTTCAAATTCACCTCAAGACTTTGAAAAAAAATTGAA TCTGTCAATGTCAAATAAAATCAGAAACAAATGTCATAATGTTACGTTAATGTTGTCAG 5 GTCGAAAAATAAAATTGCAAATAGAAATTTTGTTCCTTTTTTATTGGTTTTTATTGGTGG GAAAAATATTCCCTCTAACTGCAAAAGGGTTAATTATGTTAGAGGTAGAGTCGACGCT AGCTGGCTTGTTGTCCACAACCATTAAACCTTAAAAGCTTTAAAAGCCTTATATATTCT TTTTTTTCTTATAAAACTTAAAACCTTAGAGGCTATTTAAGTTGCTGATTTATATTAATT TTATTGTTCAAACATGAGAGCTTAGTACGTGAAACATGAGAGCTTAGTACATTAGCCAT 10 GAGAGCTTAGTACATTAGCCATGAGGGTTTAGTTCATTAAACATGAGAGCTTAGTACAT TAAACATGAGAGCTTAGTACATACTATCAACAGGTTGAACTGCTGATCTGTACAGTAG AATTGGTAAAGAGAGTTGTGTAAAATATTGAGTTCGCACATCTTGTTGTCTGATTATTG ATTTTTGGCGAAACCATTTGATCATATGACAAGATGTGTATCTACCTTAACTTAATGAT TTTGATAAAAATCATTAGGTACC 15 Schematic of the TSC-101 npDNA Transposon Vector Cassette 20 ITR MSCV promoter TCRp P2A TCRa P2A Tag CD8<x P2A CD8p        WPRE          ITR Poly A signal TCR CD34 epitope Modifications to ensure surface expression and proper a / p pairing of TCR Enables purification of engineered T cells; GMP compatible CD8 Enables functional contribution of CD4 T cells in the clinical product \______________________ / Key: CD: Cluster of Differentiation, ITR: Inverted Terminal Repeat, npDNA: Nanoplasmid DNA, MSCV: Murine Stem Cell Virus, TCR: T Cell Receptor, WPRE: Woodchuck Hepatitis Virus Post-Transcriptional Regulatory Element 25 Map of the TSC-101 npDNA Transposon Vector Cassette: 2023204645   13 Jul 2023 Virus, TCR: T Cell Receptor, TIR: Terminal Inverted Repeat, QBend: Mouse anti Human CD34 Antibody, WPRE: Woodchuck Hepatitis Virus Post-Transcriptional Regulatory Element 5 The TSC-101 npDNA Transposon is a 5,721-bp supercoiled, Nanoplasmid™ DNA (npDNA) carrying the minimal R6K bacterial replication origin and anti-sense RNA-based antibiotic-free selection marker (RNA-OUT). The inverted terminal repeats (ITRs) of the armyworm Spodoptera frugiperda transposon (required for transposase-mediated 10 integration) are connected to the two ends of the exogenous DNA sequence. The TSC-101 HA-2-specific TCR a- and P-chain genes and the codon-diversified CD8 a- and P-chain 2023204645   13 Jul 2023 genes are placed under the control of the murine stem cell virus (MSCV) promoter. The constant regions of the TCR a- and P-chains contain amino-acid substitutions that stabilize their expression on the surface of engineered T cells and help prevent mispairing with the a- and P-chains of the endogenous TCRs. These four open reading frames (TCRp, TCRa, 5 CD8a, and CD8P) are encoded on a single mRNA molecule along with the open reading frame-disabled woodchuck post-transcriptional regulatory element (WPRE), which is known to enhance gene expression (Loeb, 1999). The ribosomal skipping that takes places on the self-cleaving peptide P2A leads to production of the four separate polypeptides. The 16-amino acid CD34 epitope recognized by the mouse monoclonal antibody QBend / 10 is 10 fused to the N-terminus of the exogenous CD8 a-chain, allowing for purification of transgene-expressing cells to increase the safety and potency of the drug substance. The Nanoplasmid vector backbone (<500 base pairs) is substantially smaller than conventional plasmids (>1500 base pairs). It contains no antibiotic-resistant gene, and its replication origin (R6K) necessary for plasmid preparation supports propagation in a narrower range of 15 bacterial species than the commonly used origin pUC. * Included in Table 1 is peptide epitopes, as well as polypeptide molecules comprising an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, or more identity 20 across their full length with an amino acid sequence of any sequences listed in Table 1, or a portion thereof. Such polypeptides may have a function of the full-length peptide or polypeptide as described further herein. * Included in Table 2 are RNA nucleic acid molecules (e.g., thymines replaced with 25 uredines), nucleic acid molecules encoding orthologs of the encoded proteins, as well as DNA or RNA nucleic acid sequences comprising a nucleic acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, or more identity across their full length with the nucleic acid sequence of any sequence listed in Table 2, or a portion thereof. Such nucleic 30 acid molecules can have a function of the full-length nucleic acid as described further herein. In some embodiments, the binding proteins disclosed herein may comprise a T cell receptor (TCR), an antigen-binding fragment of a TCR, or a chimeric antigen receptor 2023204645   13 Jul 2023 (CAR). In some embodiments, the binding protein disclosed herein may comprise two polypeptide chains, each of which comprises a variable region comprising a CDR3 of a TCR alpha chain and a CDR3 of a TCR beta chain, or a CDR1, CDR2, and CDR3 of both a TCR alpha chain and a TCR beta chain. In some embodiments, a binding protein 5 comprises a single chain TCR (scTCR), which comprises both the TCR Va and TCR Vp domains, but only a single TCR constant domain (Ca or Cp). The term “chimeric antigen receptor” (CAR) refers to a fusion protein that is engineered to contain two or more naturally-occurring amino acid sequences linked together in a way that does not occur naturally or does not occur naturally in a host cell, which fusion protein can function as a 10 receptor when present on a surface of a cell. CARs encompassed by the present invention may include an extracellular portion comprising an antigen-binding domain (i.e., obtained or derived from an immunoglobulin or immunoglobulin-like molecule, such as an antibody or TCR, or an antigen binding domain derived or obtained from a killer immunoreceptor from an NK cell) linked to a transmembrane domain and one or more intracellular signaling 15   domains (optionally containing co-stimulatory domain(s)) (see, e.g., Sadelain et al. (2013) Cancer Discov. 3:388, Harris and Kranz (2016) Trends Pharmacol. Sci. 37:220, and Stone et al. (2014) Cancer Immunol. Immunother. 63:1163). In some embodiments, 1) the TCR alpha chain CDR, TCR Va domain, and / or TCR alpha chain is encoded by a TRAV, TRAJ, and / or TRAC gene or fragment thereof selected 20 from the group of TRAV, TRAJ, and TRAC genes listed in Table 1, and / or 2) the TCR beta chain CDR, TCR Vp domain, and / or TCR beta chain is encoded by a TRBV, TRBJ, and / or TRBC gene or fragment thereof selected from the group of TRBV, TRBJ, and TRBC genes listed in Table 1, and / or 3) each CDR of the binding protein has up to five amino acid substitutions, insertions, deletions, or a combination thereof as compared to the cognate 25 reference CDR sequence listed in Table 1. In some embodiments, the binding proteins (e.g., the TCR, antigen-binding fragment of a TCR, or chimeric antigen receptor (CAR)) disclosed herein is chimeric (e.g., comprises amino acid residues or motifs from more than one donor or species), humanized (e.g., comprises residues from a non-human organism that are altered or substituted so as to 30 reduce the risk of immunogenicity in a human), or human. Methods for producing engineered binding proteins, such as TCRs, CARs, and antigen-binding fragments thereof, are well-known in the art (e.g., Bowerman et al. (2009) Mol. Immunol. 5:3000; U.S. Pat. No. 6,410,319; U.S. Pat. No. 7,446,191; U.S. Pat. Publ. 2023204645   13 Jul 2023 No. 2010 / 065818; U.S. Pat. No. 8,822,647; PCT Publ. No. WO 2014 / 031687; U.S. Pat. No. 7,514,537; and Brentjens et al. (2007) Clin. Cancer Res. 73:5426). In some embodiments, the binding protein described herein is a TCR, or antigenbinding fragment thereof, expressed on a cell surface, wherein the cell surface-expressed 5 TCR is capable of more efficiently associating with a CD3 protein as compared to endogenous TCR. A binding protein encompassed by the present invention, such as a TCR, when expressed on the surface of a cell like a T cell, may also have higher surface expression on the cell as compared to an endogenous binding protein, such as an endogenous TCR. In some embodiments, provided herein is a CAR, wherein the binding 10 domain of the CAR comprises an antigen-specific TCR binding domain (see, e.g., Walseng et al. (2017) Scientific Reports 7:10713). Also provided are modified binding proteins (e.g., TCRs, antigen-binding fragments of TCRs, or CARs) that may be prepared according to well-known methods using a binding protein having one or more of the Va and / or Vp sequences disclosed herein as starting 15 material to engineer a modified binding protein that may have altered properties from the starting binding protein. A binding protein may be engineered by modifying one or more residues within one or both variable regions (i.e., Va and / or Vp), for example within one or more CDR regions and / or within one or more framework regions. Additionally or alternatively, a binding protein may be engineered by modifying residues within the 20 constant region(s). Another type of variable region modification is to mutate amino acid residues within the Va and / or Vp CDR1, CDR2 and / or CDR3 regions to thereby improve one or more binding properties (e.g., affinity) of the binding protein of interest. Site-directed mutagenesis or PCR-mediated mutagenesis may be performed to introduce the mutation(s) 25 and the effect on protein binding, or other functional property of interest, may be evaluated in in vitro, ex vivo, or in vivo assays as described herein and provided in the Examples. In some embodiments, conservative modifications (as discussed above) may be introduced. The mutations may be amino acid substitutions, additions or deletions. In some embodiments, the mutations are substitutions. Moreover, typically no more than one, two, 30 three, four or five residues within a CDR region are modified. In some embodiments, binding proteins (e.g., TCRs, antigen-binding fragments of TCRs, or CARs) described herein may possess one or more amino acid substitutions, deletions, or additions relative to a naturally occurring TCR. In some embodiments, each 2023204645   13 Jul 2023 CDR of the binding protein has up to five amino acid substitutions, insertions, deletions, or a combination thereof as compared to the cognate reference CDR sequence listed in Table 1. Conservative substitutions of amino acids are well-known and may occur naturally or may be introduced when the binding protein is recombinantly produced. Amino acid 5 substitutions, deletions, and additions may be introduced into a protein using mutagenesis methods known in the art (see, e.g., Sambrook et al. (2001) Molecular Cloning: A Laboratory Manual, 3d ed., Cold Spring Harbor Laboratory Press, NY). Oligonucleotide-directed site-specific (or segment specific) mutagenesis procedures may be employed to provide an altered polynucleotide that has particular codons altered according to the 10 substitution, deletion, or insertion desired. Alternatively, random or saturation mutagenesis techniques, such as alanine scanning mutagenesis, error prone polymerase chain reaction mutagenesis, and oligonucleotide-directed mutagenesis may be used to prepare immunogen polypeptide variants (see, e.g., Sambrook et al. supra). A variety of criteria known to the ordinarily skilled artisan indicate whether an 15 amino acid that is substituted at a particular position in a peptide or polypeptide is conservative (or similar). For example, a similar amino acid or a conservative amino acid substitution is one in which an amino acid residue is replaced with an amino acid residue having a similar side chain. Similar amino acids may be included in the following categories: amino acids with basic side chains (e.g., lysine, arginine, histidine); amino acids 20 with acidic side chains (e.g., aspartic acid, glutamic acid); amino acids with uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, histidine); amino acids with nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan); amino acids with beta-branched side chains (e.g., threonine, valine, isoleucine), and amino acids with aromatic side chains (e.g., 25 tyrosine, phenylalanine, tryptophan). Proline, which is considered more difficult to classify, shares properties with amino acids that have aliphatic side chains (e.g., leucine, valine, isoleucine, and alanine). In some embodiments, substitution of glutamine for glutamic acid or asparagine for aspartic acid may be considered a similar substitution in that glutamine and asparagine are amide derivatives of glutamic acid and aspartic acid, 30 respectively. As understood in the art "similarity" between two polypeptides is determined by comparing the amino acid sequence and conserved amino acid substitutes thereto of the polypeptide to the sequence of a second polypeptide (e.g., using GENEWORKS™, Align, the BLAST algorithm, or other algorithms described herein and practiced in the art). 2023204645   13 Jul 2023 In some embodiments, an encoded binding protein (e.g., TCR, antigen-binding fragment of a TCR, or CAR) may comprise a “signal peptide” (also known as a leader sequence, leader peptide, or transit peptide). Signal peptides target newly synthesized polypeptides to their appropriate location inside or outside the cell. A signal peptide may 5 be removed from the polypeptide during or once localization or secretion is completed. Polypeptides that have a signal peptide are referred to herein as a “pre-protein” and polypeptides having their signal peptide removed are referred to herein as “mature” proteins or polypeptides. In some embodiments, a binding protein (e.g., TCR, antigen-binding fragment of a TCR, or CAR) described herein comprises a mature Va domain, a mature Vp 10 domain, or both. In some embodiments, a binding protein (e.g., TCR, antigen-binding fragment of a TCR, or CAR) described herein comprises a mature TCR P-chain, a mature TCR a-chain, or both. In some embodiments, the binding proteins are fusion proteins comprising: (a) an extracellular component comprising a TCR or antigen-binding fragment thereof; (b) an 15 intracellular component comprising an effector domain or a functional portion thereof; and (c) a transmembrane domain connecting the extracellular and intracellular components. In some embodiments, the fusion protein is capable of binding (e.g., specifically and / or selectively) to a peptide-MHC (pMHC) complex comprising an HA-2 immunogenic peptide in the context of an MHC molecule (e.g., a MHC class I molecule). In some 20 embodiments, the MHC molecule comprises an MHC alpha chain that is an HLA serotype HLA-A* 02. In some embodiments, the HLA allele is selected from the group consisting of HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0205, HLA-A*0206, and HLA-A*0207 allele. In specific embodiments, the HLA allele is HLA-A*0201. As used herein, an “effector domain” or “immune effector domain” is an 25 intracellular portion or domain of a fusion protein or receptor that can directly or indirectly promote an immune response in a cell when receiving an appropriate signal. In some embodiments, an effector domain is from an immune cell protein or portion thereof or immune cell protein complex that receives a signal when bound (e.g., CD3Q, or when the immune cell protein or portion thereof or immune cell protein complex binds directly to a 30 target molecule and triggers signal transduction from the effector domain in an immune cell. An effector domain may directly promote a cellular response when it contains one or more signaling domains or motifs, such as an intracellular tyrosine-based activation 2023204645   13 Jul 2023 motif (IT AM), such as those found in costimulatory molecules. Without wishing to be bound by theory, it is believed that ITAMs are useful for T cell activation following ligand engagement by a T cell receptor or by a fusion protein comprising a T cell effector domain. In some embodiments, the intracellular component or functional portion thereof comprises 5 an ITAM. Exemplary immune effector domains include but are not limited to those from, CD3e, CD38, CD3^, CD25, CD79A, CD79B, CARD11, DAP10, FcRa, FcRp, FcRy, Fyn, HVEM, ICOS, Lek, LAG3, LAT, LRP, NKG2D, NOTCH1, NOTCH2, NOTCH3, NOTCH4, Wnt, ROR2, Ryk, SLAMF1, Slp76, pTa, TCRa, TCRp, TRIM, Zap70, PTCH2, or any combination thereof. In some embodiments, an effector domain comprises a 10 lymphocyte receptor signaling domain (e.g., CD3^ or a functional portion or variant thereof). In further embodiments, the intracellular component of the fusion protein comprises a costimulatory domain or a functional portion thereof selected from CD27, CD28, 4-IBB (CD137), 0X40 (CD134), CD2, CD5, ICAM-1 (CD54), LFA-1 (CD1 la / CD18), ICOS 15  (CD278), GITR, CD30, CD40, BAFF-R, HVEM, LIGHT, MKG2C, SLAMF7, NKp80, CD160, B7-H3, a ligand that binds (e.g., specifically and / or selectively) with CD83, or a functional variant thereof, or any combination thereof. In some embodiments, the intracellular component comprises a CD28 costimulatory domain or a functional portion or variant thereof (which may optionally include a LL-GG mutation at positions 186-187 of 20 the native CD28 protein (e.g, Nguyen et al. (2003) Blood 702:4320), a 4-IBB costimulatory domain or a functional portion or variant thereof, or both. In some embodiments, an effector domain comprises a CD3s endodomain or a functional (e.g, signaling) portion thereof, or a functional variant thereof. In further embodiments, an effector domain comprises a CD27 endodomain or a functional (e.g., 25 signaling) portion thereof, or a functional variant thereof. In further embodiments, an effector domain comprises a CD28 endodomain or a functional (e.g., signaling) portion thereof, or a functional variant thereof. In still further embodiments, an effector domain comprises a 4-IBB endodomain or a functional (e.g, signaling) portion thereof, or a functional variant thereof. In further embodiments, an effector domain comprises an OX40 30 endodomain or a functional (e.g, signaling) portion thereof, or a functional variant thereof. In further embodiments, an effector domain comprises a CD2 endodomain or a functional (e.g., signaling) portion thereof, or a functional variant thereof. In further embodiments, an effector domain comprises a CD5 endodomain or a functional (e.g, signaling) portion 2023204645   13 Jul 2023 thereof, or a functional variant thereof In further embodiments, an effector domain comprises an ICAM-1 endodomain or a functional (e.g., signaling) portion thereof, or a functional variant thereof. In further embodiments, an effector domain comprises a LFA-1 endodomain or a functional (e.g., signaling) portion thereof, or a functional variant thereof 5 In further embodiments, an effector domain comprises an ICOS endodomain or a functional (e.g., signaling) portion thereof, or a functional variant thereof. An extracellular component and an intracellular component encompassed by the present invention are connected by a transmembrane domain. A "transmembrane domain," as used herein, is a portion of a transmembrane protein that can insert into or span a cell 10 membrane. Transmembrane domains have a three-dimensional structure that is thermodynamically stable in a cell membrane and generally range in length from about 15 amino acids to about 30 amino acids. The structure of a transmembrane domain may comprise an alpha helix, a beta barrel, a beta sheet, a beta helix, or any combination thereof. In some embodiments, the transmembrane domain comprises or is derived from a known 15 transmembrane protein (e.g., a CD4 transmembrane domain, a CD8 transmembrane domain, a CD27 transmembrane domain, a CD28 transmembrane domain, or any combination thereof). In some embodiments, the extracellular component of the fusion protein further comprises a linker disposed between the binding domain and the transmembrane domain. 20 As used herein when referring to a component of a fusion protein that connects the binding and transmembrane domains, a “linker” may be an amino acid sequence having from about two amino acids to about 500 amino acids, which can provide flexibility and room for conformational movement between two regions, domains, motifs, fragments, or modules connected by the linker. For example, a linker encompassed by the present invention can 25 position the binding domain away from the surface of a host cell expressing the fusion protein to enable proper contact between the host cell and a target cell, antigen binding, and activation (Patel et al. (1999) Gene Therapy 6:412-419). Linker length may be varied to maximize antigen recognition based on the selected target molecule, selected binding epitope, or antigen binding domain seize and affinity (see, e.g., Guest et al. (2005) 30 Immunother. 28:203-11 and PCT Publ. No. WO 2014 / 031687). Exemplary linkers include those having a glycine-serine amino acid chain having from one to about ten repeats of GlyxSery, wherein x and y are each independently an integer from 0 to 10, provided that x 2023204645   13 Jul 2023 and y are not both 0 (e.g., (Gly4Ser)2, (Gly3Ser)2, Gly2Ser, or a combination thereof, such as ((Gly3Ser)2Gly2Ser)). Binding proteins encompassed by the present invention may, in some embodiments, be covalently linked to a moiety. In some embodiments, the covalently linked moiety 5 comprises an affinity tag or a label. The affinity tag may be selected from the group consisting of Glutathione-S-Transferase (GST), calmodulin binding protein (CBP), protein C tag, Myc tag, HaloTag, HA tag, Flag tag, His tag, biotin tag, and V5 tag. The label may be a fluorescent protein. In some embodiments, the covalently linked moiety is selected from the group consisting of an inflammatory agent, an anti-inflammatory agent, 10 a cytokine, a toxin, a cytotoxic molecule, a radioactive isotope, or an antibody such as a single-chain Fv. A binding protein may be conjugated to an agent used in imaging, research, therapeutics, theranostics, pharmaceuticals, chemotherapy, chelation therapy, targeted drug delivery, and radiotherapy. In some embodiments, a binding protein may be conjugated to 15 or fused with detectable agents, such as a fluorophore, a near-infrared dye, a contrast agent, a nanoparticle, a metal-containing nanoparticle, a metal chelate, an X-ray contrast agent, a PET agent, a metal, a radioisotope, a dye, radionuclide chelator, or another suitable material that can be used in imaging. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more detectable moieties may be linked to a binding protein. Non-limiting examples of 20 radioisotopes include alpha emitters, beta emitters, positron emitters, and gamma emitters. In some embodiments, the metal or radioisotope is selected from the group consisting of actinium, americium, bismuth, cadmium, cesium, cobalt, europium, gadolinium, iridium, lead, lutetium, manganese, palladium, polonium, radium, ruthenium, samarium, strontium, technetium, thallium, and yttrium. In some embodiments, the metal is actinium, bismuth, 25 lead, radium, strontium, samarium, or yttrium. In some embodiments, the radioisotope is actinium-225 or lead-212. In some embodiments, the near-infrared dyes are not easily quenched by biological tissues and fluids. In some embodiments, the fluorophore is a fluorescent agent emitting electromagnetic radiation at a wavelength between 650 nm and 4000 nm, such emissions being used to detect such agent. Non-limiting examples of 30 fluorescent dyes that may be used as a conjugating molecule include DyLight-680, DyLight-750, VivoTag-750, DyLight-800, IRDye-800, VivoTag-680, Cy5.5, ZQ800, or indocyanine green (ICG). In some embodiments, near infrared dyes often include cyanine dyes (e.g., Cy7, Cy5.5, and Cy5). Additional, non-limiting examples of fluorescent dyes 2023204645   13 Jul 2023 for use as a conjugating molecule in accordance with present invention include acradine orange or yellow, Alexa Fluors® (e.g., Alexa Fluor® 790, 750, 700, 680, 660, and 647) and any derivative thereof, 7-actinomycin D, 8-anilinonaphthalene-l-sulfonic acid, ATTO® dye and any derivative thereof, auramine-rhodamine stain and any derivative thereof, 5 bensantrhone, bimane, 9-10-bis(phenylethynyl)anthracene, 5,12-bis(phenylethynyl)naththacene, bisbenzimide, brainbow, calcein, carbodyfluorescein and any derivative thereof, 1-chioro-9,10-bis(phenylethynyl)anthracene and any derivative thereof, DAPI, DiOC6, DyLight® Fluors® and any derivative thereof, epicocconone, ethidium bromide, FlAsH-EDT2®, Fluo dye and any derivative thereof, FluoProbe® and 10 any derivative thereof, fluorescein and any derivative thereof, Fura® and any derivative thereof, GelGreen® and any derivative thereof, GelRed® and any derivative thereof, fluorescent proteins and any derivative thereof, m isoform proteins and any derivative thereof such as for example mCherry, hetamethine dye and any derivative thereof, hoeschst stain, iminocoumarin, indian yellow, indo-1 and any derivative thereof, laurdan, lucifer 15 yellow and any derivative thereof, luciferin and any derivative thereof, luciferase and any derivative thereof, mercocyanine and any derivative thereof, nile dyes and any derivative thereof, perylene, phloxine, phyco dye and any derivative thereof, propium iodide, pyranine, rhodamine and any derivative thereof, ribogreen, RoGFP, rubrene, stilbene and any derivative thereof, sulforhodamine and any derivative thereof, SYBR and any 20 derivative thereof, synapto-pHluorin, tetraphenyl butadiene, tetrasodium tris, Texas Red, Titan Yellow, TSQ, umbelliferone, violanthrone, yellow fluorescent protein and YOYO-1. Other suitable fluorescent dyes include, but are not limited to, fluorescein and fluorescein dyes (e.g., fluorescein isothiocyanine or FITC, naphthofluorescein, 4', 5'-dichloro-2',7'-dimethoxyfluorescein, 6-carboxyfluorescein or FAM, etc.), carbocyanine, merocyanine, 25 styryl dyes, oxonol dyes, phycoerythrin, erythrosin, eosin, rhodamine dyes (e.g., carboxytetramethyl-rhodamine or TAMRA, carboxyrhodamine 6G, carboxy-X-rhodamine (ROX), lissamine rhodamine B, rhodamine 6G, rhodamine Green, rhodamine Red, tetramethylrhodamine (TMR), etc.), coumarin and coumarin dyes (e.g., methoxycoumarin, dialkylaminocoumarin, hydroxycoumarin, aminomethylcoumarin (AMCA), etc.), Oregon 30 Green™ dyes (e.g., Oregon Green™ 488, 500, 514., etc.), Texas Red®, Texas Red®-X, SPECTRUM RED®, SPECTRUM GREEN®, cyanine dyes (e.g., CY-3, Cy-5, CY-3.5, CY-5.5, etc.), Alexa Fluor® dyes (e.g., Alexa Fluor® 350, 488, 532, 546, 568, 594, 633, 660, 680, etc.), BODIPY® dyes (e.g., BODIPY® FL, R6G, TMR, TR, 530 / 550, 558 / 568, 2023204645   13 Jul 2023 564 / 570, 576 / 589, 581 / 591, 630 / 650, 650 / 665, etc.), IRD dyes (e.g., IRD40™, IRD700™, IRD800™, etc.), and the like. Additional suitable detectable agents are well-known in the art (e.g., PCT Publ. No. PCT / US14 / 56177). Non-limiting examples of radioisotopes include alpha emitters, beta emitters, positron emitters, and gamma emitters. In some 5 embodiments, the metal or radioisotope is selected from the group consisting of actinium, americium, bismuth, cadmium, cesium, cobalt, europium, gadolinium, iridium, lead, lutetium, manganese, palladium, polonium, radium, ruthenium, samarium, strontium, technetium, thallium, and yttrium. In some embodiments, the metal is actinium, bismuth, lead, radium, strontium, samarium, or yttrium. In some embodiments, the radioisotope is 10 actinium-225 or lead-212. Binding proteins may be conjugated to a radiosensitizer or photosensitizer. Examples of radiosensitizers include but are not limited to: ABT-263, ABT-199, WEHI-539, paclitaxel, carboplatin, cisplatin, oxaliplatin, gemcitabine, etanidazole, misonidazole, tirapazamine, and nucleic acid base derivatives (e.g., halogenated purines or pyrimidines, 15 such as 5-fluorodeoxyuridine). Examples of photosensitizers include but are not limited to: fluorescent molecules or beads that generate heat when illuminated, nanoparticles, porphyrins and porphyrin derivatives (e.g., chlorins, bacteriochlorins, isobacteriochlorins, phthalocyanines, and naphthalocyanines), metalloporphyrins, metallophthalocyanines, angelicins, chalcogenapyrrillium dyes, chlorophylls, coumarins, flavins and related 20 compounds such as alloxazine and riboflavin, fullerenes, pheophorbides, pyropheophorbides, cyanines (e.g., merocyanine 540), pheophytins, sapphyrins, texaphyrins, purpurins, porphycenes, phenothiaziniums, methylene blue derivatives, naphthalimides, nile blue derivatives, quinones, perylenequinones (e.g., hypericins, hypocrellins, and cercosporins), psoralens, quinones, retinoids, rhodamines, thiophenes, 25 verdins, xanthene dyes (e.g., eosins, erythrosins, rose bengals), dimeric and oligomeric forms of porphyrins, and prodrugs such as 5-aminolevulinic acid. Advantageously, this approach allows for highly specific targeting of cells of interest (e.g., immune cells) using both a therapeutic agent (e.g., drug) and electromagnetic energy (e.g., radiation or light) concurrently. In some embodiments, the binding protein is fused with, or covalently or 30 non-covalently linked to the agent, for example, directly or via a linker. In some embodiments, the binding protein may be chemically modified. For example, a binding protein may be mutated to modify peptide properties such as detectability, stability, biodistribution, pharmacokinetics, half-life, surface charge, 2023204645   13 Jul 2023 hydrophobicity, conjugation sites, pH, function, and the like. N-methylation is one example of methylation that can occur in a binding protein encompassed by the present invention. In some embodiments, a binding protein may be modified by methylation on free amines such as by reductive methylation with formaldehyde and sodium 5 cyanoborohydride. A chemical modification may comprise a polymer, a polyether, polyethylene glycol, a biopolymer, a zwitterionic polymer, a polyamino acid, a fatty acid, a dendrimer, an Fc region, a simple saturated carbon chain such as palmitate or myristolate, or albumin. The chemical modification of a binding protein with an Fc region may be a fusion Fc-protein. 10 A polyamino acid may include, for example, a poly amino acid sequence with repeated single amino acids (e.g., poly glycine), and a poly amino acid sequence with mixed poly amino acid sequences that may or may not follow a pattern, or any combination of the foregoing. In some embodiments, the binding proteins encompassed by the present invention 15 may be modified. In some embodiments, the modifications having substantial or significant sequence identity to a parent binding protein to generate a functional variant that maintains one or more biophysical and / or biological activities of the parent binding protein (e.g., maintain pMHC binding specificity). In some embodiments, the mutation is a conservative amino acid substitution. 20          In some embodiments, binding proteins encompassed by the present invention may comprise synthetic amino acids in place of one or more naturally-occurring amino acids. Such synthetic amino acids are well-known in the art, and include, for example, aminocyclohexane carboxylic acid, norleucine, a-amino n-decanoic acid, homoserine, S-acetylaminomethyl-cysteine, trans-3- and trans-4-hydroxyproline, 4-aminophenylalanine, 4 25 nitrophenylalanine, 4-chlorophenylalanine, 4-carboxyphenylalanine, P-phenylserine P-hydroxyphenylalanine, phenylglycine, a-naphthylalanine, cyclohexylalanine, cyclohexylglycine, indoline-2-carboxylic acid, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, aminomalonic acid, aminomalonic acid monoamide, N'-benzyl-N'-methyl-lysine, N',N'-dibenzyl-lysine, 6-hydroxylysine, ornithine, a-aminocyclopentane carboxylic acid, 30 oc-aminocyclohexane carboxylic acid, a-aminocycloheptane carboxylic acid, a-(2-amino-2-norbornane)-carboxylic acid, a,y-diaminobutyric acid, ,P-diaminopropionic acid, homophenylalanine, and oc-tert-butylglycine. 2023204645   13 Jul 2023 Binding proteins encompassed by the present invention may be glycosylated, amidated, carboxylated, phosphorylated, esterified, N-acylated, cyclized (e.g., via a disulfide bridge), or converted into an acid addition salt and / or optionally dimerized or polymerized, or conjugated. 5          In some embodiments, the attachment of a hydrophobic moiety, such as to the N- terminus, the C-terminus, or an internal amino acid, may be used to extend half-life of a peptide encompassed by the present invention. In other embodiments, a binding protein may include post-translational modifications (e.g., methylation and / or amidation), which can affect, for example, serum half-life. In some embodiments, simple carbon chains (e.g., 10 by myristoylation and / or palmitylation) may be conjugated to the binding proteins. In some embodiments, the simple carbon chains may render the binding proteins easily separable from the unconjugated material. For example, methods that may be used to separate the binding proteins from the unconjugated material include, but are not limited to, solvent extraction and reverse phase chromatography. The lipophilic moieties can extend half-life 15 through reversible binding to serum albumin. The conjugated moieties may be lipophilic moieties that extend half-life of the peptides through reversible binding to serum albumin. In some embodiments, the lipophilic moiety may be cholesterol or a cholesterol derivative, including cholestenes, cholestanes, cholestadienes and oxysterols. In some embodiments, the binding proteins may be conjugated to myristic acid (tetradecanoic acid) or a derivative 20 thereof. In other embodiments, a binding protein may be coupled (e.g., conjugated) to a half-life modifying agent. Examples of half-life modifying agents include but are not limited to: a polymer, a polyethylene glycol (PEG), a hydroxyethyl starch, polyvinyl alcohol, a water soluble polymer, a zwitterionic water soluble polymer, a water soluble poly(amino acid), a water soluble polymer of proline, alanine and serine, a water soluble 25 polymer containing glycine, glutamic acid, and serine, an Fc region, a fatty acid, palmitic acid, or a molecule that binds to albumin. In some embodiments, a spacer or linker may be coupled to a binding protein, such as 1,2, 3, 4, or more amino acid residues that serve as a spacer or linker in order to facilitate conjugation or fusion to another molecule, as well as to facilitate cleavage of the peptide from such conjugated or fused molecules. In some 30 embodiments, binding proteins may be conjugated to other moieties that, for example, can modify or effect changes to the properties of the binding proteins. A binding protein may be produced recombinantly or synthetically, such as by solid-phase peptide synthesis or solution-phase peptide synthesis. Polypeptide synthesis 2023204645   13 Jul 2023 may be performed by known synthetic methods, such as using fluorenylmethyloxycarbonyl (Fmoc) chemistry or by butyloxycarbonyl (Boc) chemistry. Polypeptide fragments may be joined together enzymatically or synthetically. In an aspect encompassed by the present invention, provided herein are methods of 5 producing a binding protein described herein, comprising the steps of: (i) culturing a transformed host cell which has been transformed by a nucleic acid comprising a sequence encoding a binding protein described herein under conditions suitable to allow expression of said binding protein; and (ii) recovering the expressed binding protein. Methods useful for isolating and purifying recombinantly produced binding protein, 10 by way of example, may include obtaining supernatants from suitable host cell / vector systems that secrete the binding protein into culture media and then concentrating the media using a commercially available fdter. Following concentration, the concentrate may be applied to a single suitable purification matrix or to a series of suitable matrices, such as an affinity matrix or an ion exchange resin. One or more reverse phase HPLC steps may be 15 employed to further purify a recombinant polypeptide. These purification methods may also be employed when isolating an immunogen from its natural environment. Methods for large scale production of one or more of binding proteins described herein include batch cell culture, which is monitored and controlled to maintain appropriate culture conditions. Purification of the binding protein may be performed according to methods described 20 herein and known in the art. In any of the herein disclosed embodiments, the encoded binding protein is capable of bind to a peptide-MHC (pMHC) complex comprising an HA-2 immunogenic peptide in the context of an MHC molecule (e.g., a MHC class I molecule). In some embodiments, the MHC molecule comprises an MHC alpha chain that is an HLA serotype HLA-A*02. In 25 some embodiments, the HLA allele is selected from the group consisting of HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0205, HLA-A*0206, and HLA-A*0207 allele. A variety of assays are well-known for assessing binding affinity and / or determining whether a binding molecule binds (e.g., specifically and / or selectively) to a particular ligand (e.g., peptide antigen-MHC complex). It is within the level of a skilled 30 artisan to determine the binding affinity of a binding protein for a target, such as a T cell peptide epitope of a target polypeptide, such as by using any of a number of binding assays that are well-known in the art. For example, in some embodiments, a Biacore™ machine may be used to determine the binding constant of a complex between two proteins. The 2023204645   13 Jul 2023 dissociation constant (Kd) for the complex may be determined by monitoring changes in the refractive index with respect to time as buffer is passed over the chip. Other suitable assays for measuring the binding of one protein to another include, for example, immunoassays such as enzyme linked immunosorbent assays (ELISA) and radioimmunoas says (RIA), or 5 determination of binding by monitoring the change in the spectroscopic or optical properties of the proteins through fluorescence, UV absorption, circular dichroism, or nuclear magnetic resonance (NMR). Other exemplary assays include, but are not limited to, Western blot, ELISA, analytical ultracentrifugation, spectroscopy and surface plasmon resonance (Biacore™) analysis (see, e.g., Scatchard et al. (1949) Ann. N.Y. Acad. Sci. 10   51:660, Wilson (2002) Science 295:2103, Wolff et al. (1993) Cancer Res. 53:2560, and U.S. Pat. Nos. 5,283,173 and 5,468,614), flow cytometry, sequencing and other methods for detection of expressed nucleic acids. In one example, apparent affinity for a target is measured by assessing binding to various concentrations of tetramers, for example, by flow cytometry using labeled multimers, such as MHC-antigen tetramers. In one representative 15 example, apparent Kd of a binding protein is measured using 2-fold dilutions of labeled tetramers at a range of concentrations, followed by determination of binding curves by nonlinear regression, apparent Kd being determined as the concentration of ligand that yielded half-maximal binding. 20 III. Nucleic Acids and Vectors In an aspect encompassed by the present invention, provided herein are nucleic acid molecules that encode binding proteins (e.g., TCRs, antigen-binding fragments of the TCRs, CARs, and the like), peptides, and fragments thereof described herein. In some embodiments, the nucleic acid molecule hybridizes, under stringent 25 conditions, with the complement of a sequence with at least about at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identity, such as over the full length, to a nucleic acid encoding a polypeptide selected from the group consisting of the polypeptide sequences listed in Table 1. 30          In some embodiments, the nucleic acid molecule hybridizes, under stringent conditions, with the complement of a nucleic acid encoding a polypeptide selected from the group consisting of polypeptide sequences listed in Table 1. 2023204645   13 Jul 2023 In some embodiments, the nucleic acid molecule comprises (e.g., comprises, consists essentially of, or consists of) a nucleotide sequence encoding a polypeptide selected from the group consisting of polypeptide sequences listed in Table 1. In some embodiments, the nucleic acids comprise (e.g., comprise, consist essentially 5 of, or consist of) a nucleotide sequence encoding at least one (e.g., one, two, or three) TCR a-chain CDR set forth in Table 1. In some embodiments, the nucleic acids comprise (e.g., comprise, consist essentially of, or consist of) a nucleotide sequence encoding a TCR Va domain having an amino acid sequence that is at least about at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 10   98%, 99%, or more identity to a TCR Va domain sequence set forth in Table 1. In some embodiments, the nucleic acids comprise (e.g., comprise, consist essentially of, or consist of) a nucleotide sequence encoding a TCR a-chain having an amino acid sequence that is at least about at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identity to a TCR a-chain 15 sequence set forth in Table 1. In some embodiments, the nucleic acids comprise (e.g., comprise, consist essentially of, or consist of) a nucleotide sequence encoding at least one (e.g., one, two, or three) TCR P-chain CDR set forth in Table 1. In some embodiments, the nucleic acids comprise (e.g., comprise, consist essentially of, or consist of) a nucleotide sequence encoding a TCR Vp 20 domain having an amino acid sequence that is at least about at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identity to a TCR Vp domain sequence set forth in Table 1. In some embodiments, the nucleic acids comprise (e.g., comprise, consist essentially of, or consist of) a nucleotide sequence encoding a TCR p-chain having an amino acid sequence that is at 25 least about at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identity to a TCR p-chain sequence set forth in Table 1. The term “nucleic acid” includes “polynucleotide,” “oligonucleotide,” and “nucleic acid molecule,” and generally means a polymer of DNA or RNA, which may be single- 30 stranded or double-stranded, synthesized or obtained (e.g., isolated and / or purified) from natural sources, which may contain natural, non-natural or altered nucleotides, and which may contain a natural, non-natural or altered internucleotide linkage, such as a phosphoroamidate linkage or a phosphorothioate linkage, instead of the phosphodiester 2023204645   13 Jul 2023 found between the nucleotides of an unmodified oligonucleotide. In an embodiment, the nucleic acid comprises complementary DNA (cDNA). In some embodiments, the nucleic acids encompassed by the present invention are recombinant. As used herein, the term “recombinant” refers to (i) molecules that are 5 constructed outside living cells by joining natural or synthetic nucleic acid segments to nucleic acid molecules that may replicate in a living cell, or (ii) molecules that result from the replication of those described in (i) above. For purposes herein, the replication may be in vitro / ex vivo replication or in vivo replication. The nucleic acids can be constructed based on chemical synthesis and / or enzymatic 10 ligation reactions using procedures known in the art. See, for example, Green and Sambrook et al. supra. For example, a nucleic acid may be chemically synthesized using naturally occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed upon hybridization (e.g., phosphorothioate derivatives and acridine substituted 15 nucleotides). Examples of modified nucleotides that may be used to generate the nucleic acids include, but are not limited to, 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-(carboxyhydroxymethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1 - 20 methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-substituted adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine, 5'-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5 25 methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, 3-(3-amino-3-N-2-carboxypropyl) uracil, and 2,6-diaminopurine. Alternatively, one or more of the nucleic acids encompassed by the present invention can be purchased from companies, such as Integrated DNA Technologies (Coralville, IA). In one embodiment, the nucleic acid comprises a codon-optimized nucleotide 30 sequence. Without being bound to a particular theory or mechanism, it is believed that codon optimization of the nucleotide sequence increases the translation efficiency of the mRNA transcripts. Codon optimization of the nucleotide sequence may involve substituting a native codon for another codon that encodes the same amino acid, but can be 2023204645   13 Jul 2023 translated by tRNA that is more readily available within a cell, thus increasing translation efficiency. Optimization of the nucleotide sequence may also reduce secondary mRNA structures that would interfere with translation, thus increasing translation efficiency. In some embodiments, the nucleotide sequences described herein are codon-optimized for 5 expression in a host cell (e.g., an immune cell, such as a T cell). The present invention also provides a nucleic acid comprising a nucleotide sequence which is complementary to the nucleotide sequence of any of the nucleic acids described herein or a nucleotide sequence which hybridizes under stringent conditions to the nucleotide sequence of any of the nucleic acids described herein. 10          The nucleotide sequence which hybridizes under stringent conditions may hybridize under high stringency conditions. By “high stringency conditions” is meant that the nucleotide sequence specifically hybridizes to a target sequence (the nucleotide sequence of any of the nucleic acids described herein) in an amount that is detectably stronger than nonspecific hybridization. High stringency conditions include conditions which would 15 distinguish a polynucleotide with an exact complementary sequence, or one containing only a few scattered mismatches from a random sequence that happened to have a few small regions (e.g., 3-10 bases) that matched the nucleotide sequence. Such small regions of complementarity are more easily melted than a full-length complement of 14-17 or more bases, and high stringency hybridization makes them easily distinguishable. Relatively 20 high stringency conditions would include, for example, low salt and / or high temperature conditions, such as provided by about 0.02-0.1 M NaCl or the equivalent, at temperatures of about 50-70 °C. Such high stringency conditions tolerate little, if any, mismatch between the nucleotide sequence and the template or target strand, and are particularly suitable for detecting expression of any of the inventive TCRs. It is generally appreciated that 25 conditions may be rendered more stringent by the addition of increasing amounts of formamide. The present invention also provides a nucleic acid comprising a nucleotide sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to any of the nucleic acids 30 described herein. Typically, said nucleic acid is a DNA or RNA molecule, which may be included in a suitable vector, such as a plasmid, cosmid, episome, artificial chromosome, phage or a viral vector. 2023204645   13 Jul 2023 The terms “vector”, “cloning vector” and “expression vector” mean the vehicle by which a DNA or RNA sequence (e.g., a foreign gene) can be introduced into a host cell, so as to transform the host and promote expression (e.g., transcription and translation) of the introduced sequence. Thus, a further object encompassed by the present invention relates 5 to a vector comprising a nucleic acid encompassed by the present invention. In some embodiments, the vector is selected from the group of vectors shown in Table 2. Such vectors may comprise regulatory elements, such as a promoter, enhancer, terminator and the like, to cause or direct expression of said polypeptide upon administration to a subject. Examples of promoters and enhancers used in the expression 10 vector for animal cell include early promoter and enhancer of SV40 (Mizukami T. et al. 1987), LTR promoter and enhancer of Moloney mouse leukemia virus (Kuwana Y et al. 1987), promoter (Mason J O et al. 1985) and enhancer (Gillies S D et al. 1983) of immunoglobulin H chain and the like. Any expression vector for animal cell may be used. Examples of suitable vectors 15 include pAGE107 (Miyaji H et al. 1990), pAGE103 (Mizukami T et al. 1987), pHSG274 (Brady G et al. 1984), pKCR (O'Hare K et al. 1981), pSGl beta d2-4-(Miyaji H et al. 1990) and the like. Other representative examples of plasmids include replicating plasmids comprising an origin of replication, or integrative plasmids, such as for instance pUC, pcDNA, pBR, and the like. Representative examples of viral vector include adenoviral, 20 retroviral, lentiviral, herpes virus and AAV vectors. Such recombinant viruses may be produced by techniques known in the art, such as by transfecting packaging cells or by transient transfection with helper plasmids or viruses. Typical examples of virus packaging cells include PA317 cells, PsiCRIP cells, GPenv-positive cells, 293 cells, etc. Detailed protocols for producing such replication-defective recombinant viruses are well-known in 25 the art and may be found, for instance, in PCT Publ. WO 95 / 14785, PCT. Publ. WO 96 / 22378, U.S. Pat. No. 5,882,877, U.S. Pat. No. 6,013,516, U.S. Pat. No. 4,861,719, U.S. Pat. No. 5,278,056, and PCT Publ. WO 94 / 19478. In some embodiments, the composition comprises an expression vector comprising an open reading frame encoding a binding protein or a polypeptide described herein or a 30 fragment thereof. In some embodiments, the nucleic acid includes regulatory elements necessary for expression of the open reading frame. Such elements may include, for example, a promoter, an initiation codon, a stop codon, and a polyadenylation signal. In 2023204645   13 Jul 2023 addition, enhancers may be included. These elements may be operably linked to a sequence that encodes the binding protein, polypeptide or fragment thereof. In some embodiments, the vector further comprises nucleic acid sequence encoding CD8a and / or CD8p. In certain embodiments, the nucleic acid sequence encoding CD8a or 5 CD8P is operably linked to a nucleic acid encoding a tag (e.g., a CD34 enrichment tag). In specific embodiments, the nucleic acid sequence encoding CD8a and / or CD8P are interconnected with an internal ribosome entry site or a nucleic acid sequence encoding a self-cleaving peptide, such as P2A, E2A, F2A or T2A, etc. In some embodiments, the expression vector provided herein comprises a nucleotide 10 sequence that is at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identical to any of the nucleic acids set forth in Table 2. Examples of promoters include, but are not limited to, promoters from Simian Virus 40 (SV40), Mouse Mammary Tumor Virus (MMTV) promoter, Human Immunodeficiency 15 Virus (HIV) such as the HIV Long Terminal Repeat (LTR) promoter, Moloney virus, Cytomegalovirus (CMV) such as the CMV immediate early promoter, Epstein Barr Virus (EBV), Rous Sarcoma Virus (RSV) as well as promoters from human genes such as human actin, human myosin, human hemoglobin, human muscle creatine, and human metalothionein. Examples of suitable polyadenylation signals include but are not limited to 20 SV40 polyadenylation signals and LTR polyadenylation signals. In addition to the regulatory elements required for expression, other elements may also be included in the nucleic acid molecule. Such additional elements include enhancers. Enhancers include the promoters described herein. In some embodiments, enhancers / promoters include, for example, human actin, human myosin, human 25 hemoglobin, human muscle creatine and viral enhancers such as those from CMV, RSV and EBV. In some embodiments, the nucleic acid may be operably incorporated in a carrier or delivery vector as described further below. Useful delivery vectors include but are not limited to biodegradable microcapsules, immuno-stimulating complexes (ISCOMs) or 30 liposomes, and genetically engineered attenuated live carriers such as viruses or bacteria. In some embodiments, the vector is a viral vector, such as lentiviruses, retroviruses, herpes viruses, adenoviruses, adeno-associated viruses, vaccinia viruses, baculoviruses, 2023204645   13 Jul 2023 Fowl pox, AV-pox, modified vaccinia Ankara (MVA) and other recombinant viruses. For example, a lentivirus vector may be used to infect T cells. In some embodiments, the recombinant expression vector is capable of delivering a polynucleotide to an appropriate host cell, for example, a T cell or an antigen-presenting 5 cell, i.e., a cell that displays a peptide / MHC complex on its cell surface (e.g., a dendritic cell) and lacks CD8. In some embodiments, the host cell is a hematopoietic progenitor cell or a human immune system cell. For example, the immune system cell may be a CD4+ T cell, a CD8+ T cell, a CD4 / CD8 double negative T cell, a gd T cell, a natural killer cell, a dendritic cell, or any combination thereof. In some embodiments, wherein a T cell is the 10 host, the T cell may be naive, a central memory T cell, an effector memory T cell, or any combination thereof. The recombinant expression vectors may therefore also include, for example, lymphoid tissue-specific transcriptional regulatory elements (TREs), such as a B lymphocyte, T lymphocyte, or dendritic cell specific TREs. Lymphoid tissue specific TREs are known in the art (see, e.g., Thompson et al. (1992) Mol. Cell. Biol. 72:1043, Todd et al. 15   (1993) J. Exp. Med. 777:1663, and Penix et al. (1993) J. Exp. Med. 775:1483). In some embodiments, a recombinant expression vector comprises a nucleotide sequence encoding a TCR a chain, a TCR P chain, and / or a linker peptide. For example, in some embodiments, the recombinant expression vector comprises a nucleotide sequence encoding the full-length TCR alpha and TCR beta chains of the binding protein with a 20 linker positioned between them, wherein the nucleotide sequence encoding the beta chain is positioned 5' of the nucleotide sequence encoding the alpha chain. In some embodiments, the nucleotide sequence encodes the full-length TCR alpha and TCR beta chains with a linker positioned between them, wherein the nucleotide sequence encoding the TCR beta chain is positioned 3 ' of the nucleotide sequence encoding the TCR alpha chain. In some 25 embodiments, the full-length TCR alpha and / or TCR beta chains are replaced with fragments thereof. As described further below, another aspect encompassed by the present invention relates to a cell which has been transfected, infected or transformed by a nucleic acid and / or a vector in accordance with the present invention. A host cell may include any individual 30 cell or cell culture which may receive a vector or the incorporation of nucleic acids and / or proteins, as well as any progeny cells. The term also encompasses progeny of the host cell, whether genetically or phenotypically the same or different. Suitable host cells may depend on the vector and may include mammalian cells, animal cells, human cells, simian cells, 2023204645   13 Jul 2023 insect cells, yeast cells, and bacterial cells. These cells may be induced to incorporate the vector or other material by use of a viral vector, transformation via calcium phosphate precipitation, DEAE-dextran, electroporation, micro injection, or other methods (see, e.g., Sambrook el al. (1989) Molecular Cloning: A Laboratory Manual 2d ed. (Cold Spring 5 Harbor Laboratory)). The term “transformation” means the introduction of a “foreign” (i.e., extrinsic or extracellular) gene, DNA or RNA sequence to a host cell, so that the host cell will express the introduced gene or sequence to produce a desired substance, typically a protein or enzyme coded by the introduced gene or sequence. A host cell that receives and expresses introduced DNA or RNA has been “transformed.” 10          The nucleic acids encompassed by the present invention may be used to produce a recombinant polypeptide encompassed by the present invention in a suitable expression system. The term “expression system” means a host cell and compatible vector under suitable conditions, e.g., for the expression of a protein coded for by foreign DNA carried by the vector and introduced to the host cell. 15          Common expression systems include E. coll host cells and plasmid vectors, insect host cells and Baculovirus vectors, and mammalian host cells and vectors. Other examples of host cells include, without limitation, prokaryotic cells (such as bacteria) and eukaryotic cells (such as yeast cells, mammalian cells, insect cells, plant cells, etc.). Specific examples include E. coli, Kluyveromyces or Saccharomyces yeasts, mammalian cell lines (e.g., Vero 20 cells, CHO cells, 3T3 cells, COS cells, etc.) as well as primary or established mammalian cell cultures (e.g., produced from lymphoblasts, fibroblasts, embryonic cells, epithelial cells, nervous cells, adipocytes, etc.). Examples also include mouse SP2 / 0-Agl4 cell (ATCC CRL1581), mouse P3X63-Ag8.653 cell (ATCC CRL1580), CHO cell in which a dihydrofolate reductase gene (hereinafter referred to as “DHFR gene”) is defective (Urlaub 25 G et al (1980), rat YB2 / 3HL.P2.G11.16Ag.2O cell (ATCC CRL 1662, hereinafter referred to as “YB2 / 0 cell”), and the like. In some embodiments, the YB2 / 0 cell is used since ADCC activity of chimeric or humanized binding proteins is enhanced when expressed in this cell. The present invention also encompasses methods of producing a recombinant host 30 cell expressing binding proteins, peptides and fragments thereof encompassed by the present invention, said method comprising the steps consisting of (i) introducing in vitro or ex vivo a recombinant nucleic acid or a vector as described above into a competent host cell, (ii) culturing in vitro or ex vivo the recombinant host cell obtained and (iii), optionally, 2023204645   13 Jul 2023 selecting the cells which express said binding proteins, peptides and fragments thereof. Such recombinant host cells may be used for the diagnostic, prognostic, and / or therapeutic method encompassed by the present invention. In another aspect, the present invention provides isolated nucleic acids that 5 hybridize under selective hybridization conditions to a polynucleotide disclosed herein. Thus, the polynucleotides of this embodiment may be used for isolating, detecting, and / or quantifying nucleic acids comprising such polynucleotides. For example, polynucleotides encompassed by the present invention may be used to identify, isolate, or amplify partial or full-length clones in a deposited library. In some embodiments, the polynucleotides are 10 genomic or cDNA sequences isolated, or otherwise complementary to, a cDNA from a human or mammalian nucleic acid library. In some embodiments, the cDNA library comprises at least about 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more, or any range in between, inclusive, such as at least about 80%-100%, full-length sequences. 15 The cDNA libraries may be normalized to increase the representation of rare sequences. Low or moderate stringency hybridization conditions are typically, but not exclusively, employed with sequences having a reduced sequence identity relative to complementary sequences. Moderate and high stringency conditions may optionally be employed for sequences of greater identity. Low stringency conditions allow selective hybridization of 20 sequences having about 70% sequence identity and may be employed to identify orthologous or paralogous sequences. Optionally, polynucleotides encompassed by the present invention will encode at least a portion of a binding protein encoded by the polynucleotides described herein. The polynucleotides encompassed by the present invention embrace nucleic acid sequences that may be employed for selective hybridization 25 to a polynucleotide encoding a binding protein encompassed by the present invention (see, e.g., Ausubel, supra and Colligan, supra). IV. Host Cells In an aspect encompassed by the present invention, provided herein are host cells 30 that express the binding proteins (e.g., TCRs, antigen-binding fragments of TCRs, CARs, or fusion proteins comprising a TCR and an effector domain) described herein. In some embodiments, the host cells comprise the nucleic acids or vectors described herein. 2023204645   13 Jul 2023 In some embodiments, a polynucleotide encoding a binding protein is used to transform, transfect, or transduce a host cell (e.g., a T cell) for use in adoptive transfer therapy. Advances in nucleic acid sequencing and particular TCR sequencing have been described (e.g., Robins et al. (2009) Blood 114:4099; Robins et al. (2010) Sci. Translat. 5 Med. 2:47ra64, Robins et al. (2011) J. Imm. Meth., and Warren et al. (2011) Genome Res. 21:790) and may be employed in the course of practicing embodiments encompassed by the present invention. Similarly, methods for transfecting or transducing T cells with desired nucleic acids are well-known in the art (e.g., U.S. Pat. Publ. No. US 2004 / 0087025) as have adoptive transfer procedures using T cells of desired antigen-specificity (e.g., Schmitt et al. 10   (2009) Hum. Gen. 20:1240, Dossett et al. (2009) Mol. Then 77:742, Till et al. (2008) Blood 772:2261, Wang et al. (2007) Hum. Gene Then. 18:112, Kuball et al. (2007) Blood 709:2331, U.S. Pat. Publ. 2011 / 0243972, U.S. Pat. Publ. 2011 / 0189141, and Leen et al. (2007) Ann. Rev. Immunol. 25:243). Any suitable immune cell may be modified to include a heterologous polynucleotide 15 encompassed by the present invention, including, for example, a T cell, a NK cell, or a NK-T cell. In some embodiments, the cell may be a primary cell or a cell of a cell line. In some embodiments, a modified immune cell comprises a CD4+T cell, a CD8+ T cell, or both. For purposes herein, the T cell may be any T cell, such as a cultured T cell, e.g., a primary T cell, or a T cell from a cultured T cell line, e.g., Jurkat, SupTl, etc., or a T cell 20 obtained from a mammal. If obtained from a mammal, the T cell may be obtained from numerous sources, including but not limited to blood, bone marrow, lymph node, the thymus, or other tissues or fluids. T cells may also be enriched for or purified. In some embodiments, the T cell is a human T cell. In some embodiments, the T cell is a T cell isolated from a human. The T cell may be any type of T cell and may be of any 25 developmental stage, including but not limited to, cytotoxic lymphocyte, cytotoxic lymphocyte precursor cell, cytotoxic lymphocyte progenitor cell, cytotoxic lymphocyte stem cell, CD4+ / CD8+ double positive T cells, CD4+ helper T cells, e.g., Thl and Th2 cells, CD4+ T cells, CD8+ T cells (e.g., cytotoxic T cells), tumor infdtrating lymphocytes (TILs), memory T cells (e.g., central memory T cells and effector memory T cells), naive T cells, 30 and the like. Any appropriate method may be used to transfect or transduce the cells, for example, T cells, or to administer the nucleotide sequences or compositions encompassed by methods described herein. Methods for delivering polynucleotides to host cells include, 2023204645   13 Jul 2023 for example, use of cationic polymers, lipid-like molecules, and certain commercial products such as, for example, in vivo-jetPEI®. Other methods include ex vivo transduction, injection, electroporation, DEAE-dextran, sonication loading, liposome-mediated transfection, receptor-mediated transduction, microprojectile bombardment, 5 transposon-mediated transfer, and the like. Still further methods of transfecting or transducing host cells employ vectors, described in further detail herein. Modified immune cells as described herein may be functionally characterized using methodologies for assaying T cell activity, including determination of T cell binding, activation or induction and also including determination of T cell responses that are 10 antigen-specific. Examples include determination of T cell proliferation, T cell cytokine release, antigen-specific T cell stimulation, MHC restricted T cell stimulation, CTL activity (e.g., by detecting 51Cr release from pre-loaded target cells), changes in T cell phenotypic marker expression, and other measures of T-cell functions. Procedures for performing these and similar assays may be found, for example, in 15 Lefkovits (Immunology Methods Manual: Hie Comprehensive Sourcebook of Techniques, 1998), as well as Current Protocols in Immunology, Weir, (1986) Handbook of Experimental Immunology, Blackwell Scientific, Boston, MA; Mishell and Shigii (eds.) (1979) Selected Methods in Cellular Immunology, Freeman Publishing, San Francisco, CA; Green and Reed (1998) Science 281:1309, and references cited therein. 20          In some embodiments, apparent affinity for a binding protein, such as a TCR or antigen-binding portion thereof, may be measured by assessing binding to various concentrations of MHC multimers. “MHC-peptide multimer staining” refers to an assay used to detect antigen-specific T cells, which, in some embodiments, features a tetramer of MHC molecules, each comprising an identical peptide having an amino acid sequence that 25 is cognate (e.g., identical or related to) at least one antigen (e.g., an HA-2 immunogenic peptide), wherein the complex is capable of binding to a binding protein, such as a TCR or antigen-binding portion thereof, that recognizes the cognate antigen. Each of the MHC molecules may be tagged with a biotin molecule. Biotinylated MHC / peptides may be multimerized (e.g., tetramerized) by the addition of streptavidin, which may be 30 fluorescently labeled. The multimer may be detected by flow cytometry via the fluorescent label. In some embodiments, a pMHC multimer assay is used to detect or select enhanced affinity binding protein, such as a TCR or antigen-binding portion thereof, encompassed by the present 2023204645   13 Jul 2023 invention. In some examples, apparent Kd of a binding protein, such as a TCR or antigenbinding portion thereof, is measured using 2-fold dilutions of labeled multimers at a range of concentrations, followed by determination of binding curves by non-linear regression, apparent Kd being determined as the concentration of ligand that yielded half-maximal 5 binding. Levels of cytokines may be determined using methods described herein, such as ELISA, ELISPOT, intracellular cytokine staining, and flow cytometry and combinations thereof (e.g., intracellular cytokine staining and flow cytometry). Immune cell proliferation and clonal expansion resulting from an antigen-specific 10 elicitation or stimulation of an immune response may be determined by isolating lymphocytes, such as circulating lymphocytes in samples of peripheral blood cells or cells from lymph nodes, stimulating the cells with antigen, and measuring cytokine production, cell proliferation and / or cell viability, such as by incorporation of tritiated thymidine or non-radioactive assays, such as MTT assays and the like. The effect of an immunogen 15 described herein on the balance between a Thl immune response and a Th2 immune response may be examined, for example, by determining levels of Thl cytokines, such as IFN-g, IL-12, IL-2, and TNF-b, and Type 2 cytokines, such as IL-4, IL-5, IL-9, IL-10, and IL-13. A host cell encompassed by the present invention may comprise a single 20 polynucleotide that encodes a binding protein as described herein, or the binding protein may be encoded by more than one polynucleotide. In other words, components or portions of a binding protein may be encoded by two or more polynucleotides, which may be contained on a single nucleic acid molecule or may be contained on two or more nucleic acid molecules. 25          In some embodiments, a polynucleotide encoding two or more components or portions of a binding protein encompassed by the present invention comprises the two or more coding sequences operatively associated in a single open reading frame. Such an arrangement can advantageously allow coordinated expression of desired gene products, such as, for example, contemporaneous expression of alpha- and beta-chains of a TCR, 30 such that they are produced in about a 1:1 ratio. In some embodiments, two or more substituent gene products of a binding protein encompassed by the present invention, such as a TCR (e.g., alpha- and beta-chains) or CAR, are expressed as separate molecules and associate post-translationally. In further embodiments, two or more substituent gene 2023204645   13 Jul 2023 products of a binding protein encompassed by the present invention are expressed as a single peptide with the parts separated by a cleavable or removable segment. For instance, self-cleaving peptides useful for expression of separable polypeptides encoded by a single polynucleotide or vector are known in the art and include, for example, a porcine 5 teschovirus-1 2 A (P2A) peptide, a thoseaasigna virus 2A (T2A) peptide, an equine rhinitis A virus (ERAV) 2A (E2A) peptide, and a foot-and-mouth disease vims 2A (F2A) peptide. In some embodiments, a binding protein encompassed by the present invention comprises one or more junction amino acids. “Junction amino acids” or “junction amino acid residues” refer to one or more (e.g., 2 to about 10) amino acid residues between two 10 adjacent motifs, regions or domains of a polypeptide, such as between a binding domain and an adjacent constant domain or between a TCR chain and an adjacent self-cleaving peptide. Junction amino acids can result from the design of a construct that encodes a fusion protein (e.g., amino acid residues resulting from the use of a restriction enzyme site during the construction of a nucleic acid molecule encoding a fusion protein), or from 15 cleavage of, for example, a self-cleaving peptide adjacent one or more domains of an encoded binding protein encompassed by the present invention (e.g., a P2A peptide disposed between a TCR a-chain and a TCR 0-chain, the self-cleavage of which can leave one or more junction amino acids in the a-chain, the TCR 0-chain, or both). Engineered immune cells encompassed by the present invention may be 20 administered as therapies for, e.g., a non-malignant disorder, a hyperproliferative disorder, or a relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen. In some circumstances, it may be desirable to reduce or stop the activity associated with a cellular immunotherapy. Thus, in some embodiments, an engineered immune cell encompassed by the present invention comprises a heterologous 25 polynucleotide encoding a binding protein and an accessory protein, such as a safety switch protein, which can be targeted using a cognate drug or other compound to selectively modulate the activity (e.g., lessen or ablate) of such cells when desirable. Safety switch proteins used in this regard include, for example, a truncated EGF receptor polypeptide (huEGFRt) that is devoid of extracellular N-terminal ligand binding domains and 30 intracellular receptor tyrosine kinase activity but retains the native amino acid sequence, type I transmembrane cell surface localization, and a conformationally intact binding epitope for pharmaceutical-grade anti-EGFR monoclonal antibody, cetuximab (Erbitux) tEGF receptor (tEGFr; Wang et al. (2011) Blood 118:1255-1263), a caspase polypeptide 2023204645   13 Jul 2023 (e.g., iCasp9; Straathof et al. (2005) Blood 105:4247-4254, Di Stasi et al. (2011) N. Engl. J. Med. 365:1673-1683, Zhou and Brenner (2016) Hematol. pii:S0301-472X:30513-30516), RQR8 (Philip et al. (2014) Blood 124:1277-1287), and a human c-myc protein tag (Kieback et al. (2008) Proc. Natl. Acad. Sci. USA 105:623-628) 5          Other accessory components useful for therapeutic cells comprise a tag or selection marker (e.g., a CD34 enrichment tag) that allows the cells to be identified, sorted, isolated, enriched, or tracked. For example, marked immune cells having desired characteristics (e.g., an antigen-specific TCR and a safety switch protein) may be sorted away from unmarked cells in a sample and more efficiently activated and expanded for inclusion in a 10 therapeutic product of desired purity. As used herein, the term “selection marker" comprises a nucleic acid construct that confers an identifiable change to a cell permitting detection and positive selection of immune cells transduced with a polynucleotide comprising a selection marker. For example, RQR is a selection marker that comprises a major extracellular loop of CD20 and 15 two minimal CD34 binding sites. In some embodiments, an RQR-encoding polynucleotide comprises a polynucleotide that encodes the 16 amino acid CD34 minimal epitope. In some embodiments, such as certain embodiments provided in the examples herein, the CD34 minimal epitope is incorporated at the amino terminal position of the CD8 stalk domain (Q8). In further embodiments, the CD34 minimal binding site sequence may be 20 combined with a target epitope for CD20 to form a compact marker / suicide gene for T cells (RQR8) (Philip et al. 2014). This construct allows for the selection of immune cells expressing the construct, with for example, CD34-specific antibody bound to magnetic beads (Miltenyi) and that utilizes clinically accepted pharmaceutical antibody, rituximab, that allows for the selective deletion of a transgene expressing engineered T cell (e.g., 25 Philip et al. (2014) Blood 124:1277-1287, U.S. Pat. Publ. 2015-0093401, and U.S. Pat. Publ. 2018-0051089). Further exemplary selection markers include several truncated type I transmembrane proteins normally not expressed on T cells: the truncated low-affinity nerve growth factor, truncated CD 19, and truncated CD34 (e.g., Di Stasi et al. (2011) N. Engl. J. 30 Med. 365:1673-1683, Mavilio et a / . (1994) Blood 83:1988-1997, and Fehse et al. (2000) Mol. Ther. 7:448-456). A particularly attractive feature of CD 19 and CD34 is the availability of the off-the-shelf Miltenyi CliniMACs™ selection system that can target these markers for clinical-grade sorting. However, CD 19 and CD34 are relatively large 2023204645   13 Jul 2023 surface proteins that may tax the vector packaging capacity and transcriptional efficiency of an integrating vector. Surface markers containing the extracellular, non-signaling domains or various proteins (e.g., CD 19, CD34, LNGFR, etc.) also may be employed. Any selection marker may be employed and should be acceptable for good manufacturing practices. In 5 some embodiments, selection markers are expressed with a polynucleotide that encodes a gene product of interest (e.g., a binding protein encompassed by the present invention, such as a TCR or CAR, or antigen-binding fragment thereof). Further examples of selection markers include, for example, reporters such as GFP, EGFP, P-gal or chloramphenicol acetyltransferase (CAT). In some embodiments, a selection marker, such as, for example, 10 CD34 is expressed by a cell and the CD34 may be used to select enrich for, or isolate (e.g., by immunomagnetic selection) the transduced cells of interest for use in the methods described herein. As used herein, a CD34 marker is distinguished from an anti-CD34 antibody, or, for example, a scFv, TCR, or other antigen recognition moiety that binds to CD34. 15          In some embodiments, a selection marker comprises an RQR polypeptide, a truncated low-affinity nerve growth factor (tNGFR), a truncated CD 19 (tCD19), a truncated CD34 (tCD34), or any combination thereof. By way of background, inclusion of CD4+ T cells in an immunotherapy cell product can provide antigen-induced IL-2 secretion and augment persistence and function of 20 transferred cytotoxic CD8+ T cells (e.g., Kennedy et al. (2008) Immunol. Rev. 222:129 and Nakanishi et al. Nature (2009) 52:510). In some embodiments, a class I-restricted TCR in CD4+ T cells may require the transfer of a CD8 co-receptor to enhance sensitivity of the TCR to class IHLA peptide complexes. CD4 co-receptors differ in structure to CD8 and cannot effectively substitute for CD8 co-receptors (e.g., Stone & Kranz (2013) Front. 25 Immunol. 4:244 and Cole et al. (2012) Immunology 737:139). Thus, another accessory protein for use in the compositions and methods encompassed by the present invention comprises a CD8 co-receptor or component thereof. Engineered immune cells comprising a heterologous polynucleotide encoding a binding protein encompassed by the present invention may, in some embodiments, further comprise a heterologous polynucleotide 30 encoding a CD8 co-receptor protein, or a beta-chain or alpha-chain component thereof. A host cell may be efficiently transduced to contain, and may efficiently express, a single polynucleotide that encodes the binding protein, safety switch protein, selection marker, and CD8 co-receptor protein. 2023204645   13 Jul 2023 In one embodiment, the host cell encompassed by the present invention further includes a nucleic acid encoding a co-stimulatory molecule, such that the modified T cell expresses the co-stimulatory molecule. In some embodiments, the co-stimulatory domain is selected from CD3, CD27, CD28, CD83, CD86, CD127, 4-1BB, 4-1BBL, PD1 and PD1L. 5          In any of the foregoing embodiments, a host cell that express the binding protein described herein may be a universal immune cell. A “universal immune cell” comprises an immune cell that has been modified to reduce or eliminate expression of one or more endogenous genes that encode a polypeptide product selected from PD-1, LAG-3, CTLA4, TIM3, TIGIT, an HLA molecule, a TCR molecule, or any combination thereof. Without 10 wishing to be bound by theory, certain endogenously expressed immune cell proteins may downregulate the immune activity of the modified immune cells (e.g., PD-1, LAG-3, CTLA4, TIGIT), or may interfere with the binding activity of a heterologously expressed binding protein encompassed by the present invention (e.g., an endogenous TCR that binds a non-HA-2 antigen and interferes with the modified immune cell binding to a target cell 15 that expresses an HA-2 antigen such as an HA-2 immunogenic peptide comprising the amino acid sequence YIGEVLVSV or YIGEVLVSM in the context of a MHC molecule. Further, endogenous proteins (e.g., immune cell proteins, such as an HLA allele) expressed on a donor immune cell may be recognized as foreign by an allogeneic host, which may result in elimination or suppression of the modified donor immune cell by the allogeneic 20 host. Accordingly, decreasing or eliminating expression or activity of such endogenous genes or proteins can improve the activity, tolerance, or persistence of the modified immune cells in an autologous or allogeneic host setting, and allows universal administration of the cells (e.g., to any recipient regardless of HLA type). In some 25 embodiments, cells in accordance with the present invention are syngeneic, meaning that they are genetically identical or sufficiently identical and immunologically compatible as to allow for transplantation. In some embodiments, a universal immune cell is a donor cell (e.g., allogeneic) or an autologous cell. In some embodiments, a modified immune cell (e.g., a universal immune cell) encompassed by the present invention comprises a 30 chromosomal gene knockout of one or more of a gene that encodes PD-1, LAG-3, CTLA4, TIM3, TIGIT, an HLA component (e.g., a gene that encodes an al macroglobulin, an a2 macroglobulin, an a3 macroglobulin, a pl microglobulin, or a P2 microglobulin), or a TCR component (e.g., a gene that encodes a TCR variable region or a TCR constant region) (see, 2023204645   13 Jul 2023 e.g., Torikai el al. (2016) Nature Sei. Rep. 6:21757; Torikai et al. (2012) Blood 179:5697; and Torikai et al. (2013) Blood 722:1341, which also provide representative, exemplary gene editing techniques, compositions, and adoptive cell therapies useful according to the present invention). 5          As used herein, the term “chromosomal gene knockout” refers to a genetic alteration or introduced inhibitory agent in a host cell that prevents (e.g., reduces, delays, suppresses, or abrogates) production, by the host cell, of a functionally active endogenous polypeptide product. Alterations resulting in a chromosomal gene knockout may include, for example, introduced nonsense mutations (including the formation of premature stop codons), 10 missense mutations, gene deletion, and strand breaks, as well as the heterologous expression of inhibitory nucleic acid molecules that inhibit endogenous gene expression in the host cell. In some embodiments, a chromosomal gene knock-out or gene knock-in may be made by chromosomal editing of a host cell. Chromosomal editing may be performed 15 using, for example, endonucleases. As used herein “endonuclease” refers to an enzyme capable of catalyzing cleavage of a phosphodiester bond within a polynucleotide chain. In some embodiments, an endonuclease is capable of cleaving a targeted gene thereby inactivating or “knocking out” the targeted gene. An endonuclease may be a naturally occurring, recombinant, genetically modified, or fusion endonuclease. The nucleic acid 20 strand breaks caused by the endonuclease are commonly repaired through the distinct mechanisms of homologous recombination or non-homologous end joining (NHEJ). During homologous recombination, a donor nucleic acid molecule may be used for a donor gene "knock-in", for target gene "knock-out", and optionally to inactivate a target gene through a donor gene knock in or target gene knock out event. NHEJ is an error-prone 25 repair process that often results in changes to the DNA sequence at the site of the cleavage, e.g., a substitution, deletion, or addition of at least one nucleotide. NHEJ may be used to “knock-out” a target gene. Examples of endonucleases include zinc finger nucleases, TALE-nucleases, CRISPR-Cas nucleases, meganucleases, and megaTALs. As used herein, a “zinc finger nuclease” (ZFN) refers to a fusion protein comprising 30 a zinc finger DNA-binding domain fused to a non-specific DNA cleavage domain, such as a Fokl endonuclease. Each zinc finger motif of about 30 amino acids binds to about 3 base pairs of DNA, and amino acids at certain residues maybe changed to alter triplet sequence specificity (e.g., Desjarlais et al. (1993) Proc. Natl. Acad. Sci. 90:2256-2260 and Wolfe et 2023204645   13 Jul 2023 al. (1999) ]. Mol. Biol. 255:1917-1934). Multiple zinc finger motifs may be linked in tandem to create binding specificity to desired DNA sequences, such as regions having a length ranging from about 9 to about 18 base pairs. By way of background, ZFNs mediate genome editing by catalyzing the formation of a site-specific DNA double strand break 5 (DSB) in the genome, and targeted integration of a transgene comprising flanking sequences homolo...

Claims

1. A method of detecting the presence or absence of an HA-2 antigen and / or a cellexpressing HA-2, optionally wherein the cell is a hyperproliferative cell, comprising detecting the presence or absence of said HA-2 antigen in a sample by use of an HA-2 (YIGEVLVSV) peptide-MHC (HLA-A*02) (pMHC) complex binding protein comprising:a) a T cell receptor (TCR) alpha chain variable domain comprising CDR1 having residues 47-53 of SEQ ID NO: 93, CDR2 having residues 71-78 of SEQ ID NO: 93, and CDR3 having residues 112-124 of SEQ ID NO: 93; andb) a TCR beta chain variable domain comprising CDR1 having residues 44-49 of SEQ ID NO: 92, CDR2 having residues 67-71 of SEQ ID NO: 92, and CDR3 having residues 108-126 of SEQ ID NO: 92,or a host cell expressing the binding protein,wherein detection of the HA-2 antigen is indicative of the presence of an HA-2 antigen and / or cell expressing HA-2.

2. The method of claim 1, wherein the binding protein comprises:i)a) a TCR alpha chain variable (Va) domain comprising residues 1-135 of SEQ ID NO: 93; andb) a TCR beta chain variable (V p) domain comprising residues 1-136 of SEQ ID NO: 92;ii)a) a TCR alpha chain variable (Va) domain comprising residues 1-135 of SEQ ID NO: 93; andb) a TCR beta chain sequence comprising i) the sequence of SEQ ID NO: 92 or ii) the sequence of SEQ ID NO: 92, except with the following five substitutions:E153K, S157A, F268I, V271A, and Q274H;iii)a) a TCR alpha chain sequence comprising the sequence of SEQ ID NO: 93; and b) a TCR beta chain variable (Vp) domain comprising residues 1-136 of SEQ ID NO: 92;2023204645   23 Aug 2026iv)a) a TCR alpha chain variable (Va) domain comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to residues 1-135 of SEQ ID NO: 93; andb) a TCR beta chain variable (V p) domain comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to residues 1-136 of SEQ ID NO: 92;v)a) a TCR alpha chain variable (Va) domain comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to residues 1-135 of SEQ ID NO: 93; andb) a TCR beta chain sequence comprising i) an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 92 or ii) an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 92, except with the following five substitutions: E153K, S157A, F268I, V271A, and Q274H; orvi)a) a TCR alpha chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 93; and b) a TCR beta chain variable (Vp) domain comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to residues 1-136 of SEQ ID NO: 92.

3. The method of claim 1 or 2, wherein the binding protein comprises:2023204645   23 Aug 2026i)a) a TCR alpha chain sequence comprising the sequence of SEQ ID NO: 93; and b) a TCR beta chain sequence comprising the sequence of SEQ ID NO: 92; or ii)a) a TCR alpha chain sequence comprising the sequence of SEQ ID NO: 93; and b) a TCR beta chain sequence comprising the sequence of SEQ ID NO: 92, except with the following five substitutions: E153K, S157A, F268I, V271A, and Q274H;iii)a) a TCR alpha chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 93; andb) a TCR beta chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 92; or iv)a) a TCR alpha chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 93; and b) a TCR beta chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 92, except with the following five substitutions: E153K, S157A, F268I, V271A, and Q274H.

4. The method of any one of claims 1-3, wherein 1) the TCR alpha chain or TCR Vadomain is encoded by a TRAV38-2DV8 and TRAJ11 gene and / or 2) TCR beta chain or TCR Vp domain is encoded by a TRBV30 and TRBJ2-3 gene.

5. The method of any one of claims 1-4, wherein:a) the binding protein, or the host cell, forms a complex with the HA-2 peptide in the context of an MHC molecule, and the complex is detected in the form of fluorescence activated cell sorting (FACS), enzyme linked immunosorbent assay (ELISA), radioimmune assay (RIA), immunochemically, Western blot, or intracellular flow assay;2023204645   23 Aug 2026b) the method further comprises obtaining the sample from a subject; and / orc) the method further comprises confirming cells expressing HA-2 by bone marrow biopsy.

6. A method of detecting the level of a non-malignant disorder, a hyperproliferativedisorder, or a relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen in a subject, comprising:a) contacting a sample obtained from the subject with an HA-2 (YIGEVLVSV) peptide-MHC (HLA-A*02) (pMHC) complex binding protein comprising:i) a T cell receptor (TCR) alpha chain variable domain comprising CDR1 having residues 47-53 of SEQ ID NO: 93, CDR2 having residues 71-78 of SEQ ID NO: 93, and CDR3 having residues 112-124 of SEQ ID NO: 93; andii) a TCR beta chain variable domain comprising CDR1 having residues 44-49 of SEQ ID NO: 92, CDR2 having residues 67-71 of SEQ ID NO: 92, and CDR3 having residues 108-126 of SEQ ID NO: 92, ora host cell expressing the binding protein, or a population of host cells expressing the binding protein; andb) detecting the level of reactivity,wherein a higher level of reactivity compared to a control level indicates the level of a non-malignant disorder, a hyperproliferative disorder, or a relapse of a hyperproliferative disorder characterized by expression of the HA-2 antigen in the subject.

7. The method of claim 6, wherein the binding protein comprises:i)a) a TCR alpha chain variable (Va) domain comprising residues 1-135 of SEQ ID NO: 93; andb) a TCR beta chain variable (V p) domain comprising residues 1-136 of SEQ ID NO: 92;ii)a) a TCR alpha chain variable (Va) domain comprising residues 1-135 of SEQ ID NO: 93; and2023204645   23 Aug 2026b) a TCR beta chain sequence comprising i) the sequence of SEQ ID NO: 92 or ii) the sequence of SEQ ID NO: 92, except with the following five substitutions: E153K, S157A, F268I, V271A, and Q274H; oriii)a) a TCR alpha chain sequence comprising the sequence of SEQ ID NO: 93; and b) a TCR beta chain variable (Vp) domain comprising residues 1-136 of SEQ ID NO: 92 iv)a) a TCR alpha chain variable (Va) domain comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to residues 1-135 of SEQ ID NO: 93; andb) a TCR beta chain variable (Vp) domain comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to residues 1-136 of SEQ ID NO: 92;v)a) a TCR alpha chain variable (Va) domain comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to residues 1-135 of SEQ ID NO: 93; andb) a TCR beta chain sequence comprising i) an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 92 or ii) an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 92, except with the following five substitutions: E153K, S157A, F268I, V271A, and Q274H; orvi)a) a TCR alpha chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 93; and2023204645   23 Aug 2026b) a TCR beta chain variable (Vp) domain comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to residues 1-136 of SEQ ID NO: 92.

8. The method of claim 6 or 7, wherein the binding protein comprises:i)a) a TCR alpha chain sequence comprising the sequence of SEQ ID NO: 93; and b) a TCR beta chain sequence comprising the sequence of SEQ ID NO: 92; or ii)a) a TCR alpha chain sequence comprising the sequence of SEQ ID NO: 93; and b) a TCR beta chain sequence comprising the sequence of SEQ ID NO: 92, except with the following five substitutions: E153K, S157A, F268I, V271A, and Q274H;iii)a) a TCR alpha chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 93; andb) a TCR beta chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 92; or iv)a) a TCR alpha chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 93; and b) a TCR beta chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 92, except with the following five substitutions: E153K, S157A, F268I, V271A, and Q274H.

9. The method of any one of claims 6-8, wherein 1) the TCR alpha chain or TCR V domainis encoded by a TRAV38-2DV8 and TRAJ11 gene and / or 2) TCR beta chain or TCR V domain is encoded by a TRBV30 and TRBJ2-3 gene.2023204645   23 Aug 202610. The method of any one of claims 6-8, wherein the control level is:a) a reference number; orb) a level of a subject without the non-malignant disorder, a hyperproliferative disorder, or a relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen.

11. A method for monitoring the progression of a non-malignant disorder, a hyperproliferative disorder, or a relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen in a subject, the method comprising:a) detecting in a subject sample at a first point in time the level of the HA-2 antigen or the cell of interest expressing HA-2 , according to any one of claims 1-10;b) repeating step a) at a subsequent point in time; andc) comparing the level of HA-2antigen or the cell of interest expressing HA-2detected in steps a) and b) to monitor the progression of a non-malignant disorder, a hyperproliferative disorder, or a relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen in the subject, wherein an absent or reduced level of the HA-2antigen or the cell of interest expressing HA-2 detected in step b) compared to step a) indicates an inhibited progression of the non-malignant disorder, the hyperproliferative disorder, or the relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen in the subject.

12. The method of claim 11, wherein between the first point in time and the subsequent point in time, the subject has undergone treatment to treat the non-malignant disorder, the hyperproliferative disorder, or the relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen.

13. A method of assessing the efficacy of a therapy for a non-malignant disorder, a hyperproliferative disorder, or a relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen comprising:a) determining the presence or level of reactivity between a sample obtained from the subject and an HA-2 (YIGEVLVSV) peptide-MHC (HLA-A*02) (pMHC) complex binding protein comprising:2023204645   23 Aug 2026i) a T cell receptor (TCR) alpha chain variable domain comprising CDR1 having residues 47-53 of SEQ ID NO: 93, CDR2 having residues 71-78 of SEQ ID NO: 93, and CDR3 having residues 112-124 of SEQ ID NO: 93; andii) a TCR beta chain variable domain comprising CDR1 having residues 44-49 of SEQ ID NO: 92, CDR2 having residues 67-71 of SEQ ID NO: 92, and CDR3 having residues 108-126 of SEQ ID NO: 92,a host cell expressing the binding protein, or a population of host cells expressing the binding protein, in a first sample obtained from a subject prior to providing at least a portion of the therapy for the non-malignant disorder, the hyperproliferative disorder, or the relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen to the subject, and b) determining the presence or level of reactivity between a sample obtained from the subject and the binding protein, a host cell expressing the binding protein, or a population of host cells expressing the binding protein, in a second sample obtained from the subject following provision of the portion of the therapy for the non-malignant disorder, the hyperproliferative disorder, or the relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen,wherein the absence or a reduced level of reactivity in the second sample, relative to the first sample, is an indication that the therapy is efficacious for treating the non-malignant disorder, the hyperproliferative disorder, or the relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen in the subject.

14. The method of claim 13, wherein the binding protein comprises:i)a) a TCR alpha chain variable (Va) domain comprising residues 1-135 of SEQ ID NO: 93; andb) a TCR beta chain variable (V p) domain comprising residues 1-136 of SEQ ID NO: 92;ii)a) a TCR alpha chain variable (Va) domain comprising residues 1-135 of SEQ ID NO: 93; and2023204645   23 Aug 2026b) a TCR beta chain sequence comprising i) the sequence of SEQ ID NO: 92 or ii) the sequence of SEQ ID NO: 92, except with the following five substitutions: E153K, S157A, F268I, V271A, and Q274H; oriii)a) a TCR alpha chain sequence comprising the sequence of SEQ ID NO: 93; and b) a TCR beta chain variable (Vp) domain comprising residues 1-136 of SEQ ID NO: 92;iv)a) a TCR alpha chain variable (Va) domain comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to residues 1-135 of SEQ ID NO: 93; andb) a TCR beta chain variable (Vp) domain comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to residues 1-136 of SEQ ID NO: 92;v)a) a TCR alpha chain variable (Va) domain comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to residues 1-135 of SEQ ID NO: 93; andb) a TCR beta chain sequence comprising i) an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 92 or ii) an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 92, except with the following five substitutions: E153K, S157A, F268I, V271A, and Q274H; orvi)2023204645   23 Aug 2026a) a TCR alpha chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 93; and b) a TCR beta chain variable (Vp) domain comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to residues 1-136 of SEQ ID NO: 92.

15. The method of claim 13 or 14, wherein the binding protein comprises: i)a) a TCR alpha chain sequence comprising the sequence of SEQ ID NO: 93; and b) a TCR beta chain sequence comprising the sequence of SEQ ID NO: 92; or ii)a) a TCR alpha chain sequence comprising the sequence of SEQ ID NO: 93; and b) a TCR beta chain sequence comprising the sequence of SEQ ID NO: 92, except with the following five substitutions: E153K, S157A, F268I, V271A, and Q274H;iii)a) a TCR alpha chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 93; andb) a TCR beta chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 92; or iv)a) a TCR alpha chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 93; and b) a TCR beta chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 92, except with the following five substitutions: E153K, S157A, F268I, V271A, and Q274H.2023204645   23 Aug 202616. The method of any one of claims 13-15, wherein 1) the TCR alpha chain or TCR V domain is encoded by a TRAV38-2DV8 and TRAJ11 gene and / or 2) TCR beta chain or TCR V domain is encoded by a TRBV30 and TRBJ2-3 gene.

17. The method of any one of claims 13-16, wherein:i) the level of reactivity is indicated by a) the presence of binding and / or b) T cell activation and / or effector function, optionally wherein the T cell activation or effector function is T cell proliferation, killing, or cytokine release; and / orii) the T cell binding, activation, and / or effector function is detected using fluorescence activated cell sorting (FACS), enzyme linked immunosorbent assay (ELISA), radioimmune assay (RIA), immunochemically, Western blot, or intracellular flow assay.

18. A method of preventing and / or treating a non-malignant disorder, a hyperproliferative disorder or a relapse of a hyperproliferative disorder characterized by expression of an HA-2 antigen in a subject comprising administering to the subject a therapeutically effective amount of a composition comprising cells expressing an HA-2 (YIGEVLVSV) peptide-MHC (HLA-A*02) (pMHC) complex binding protein comprising:a) a T cell receptor (TCR) alpha chain variable domain comprising CDR1 having residues 47-53 of SEQ ID NO: 93, CDR2 having residues 71-78 of SEQ ID NO: 93, and CDR3 having residues 112-124 of SEQ ID NO: 93; andb) a TCR beta chain variable domain comprising CDR1 having residues 44-49 of SEQ ID NO: 92, CDR2 having residues 67-71 of SEQ ID NO: 92, and CDR3 having residues 108-126 of SEQ ID NO: 92.

19. The method of claim 18, wherein the binding protein comprises:i)a) a TCR alpha chain variable (Va) domain comprising residues 1-135 of SEQ ID NO: 93; andb) a TCR beta chain variable (V p) domain comprising residues 1-136 of SEQ ID NO: 92;ii)2023204645   23 Aug 2026a) a TCR alpha chain variable (Va) domain comprising residues 1-135 of SEQ ID NO: 93; andb) a TCR beta chain sequence comprising i) the sequence of SEQ ID NO: 92 or ii) the sequence of SEQ ID NO: 92, except with the following five substitutions: E153K, S157A, F268I, V271A, and Q274H; oriii)a) a TCR alpha chain sequence comprising the sequence of SEQ ID NO: 93; and b) a TCR beta chain variable (V p) domain comprising residues 1-136 of SEQ ID NO: 92;iv)a) a TCR alpha chain variable (Va) domain comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to residues 1-135 of SEQ ID NO: 93; andb) a TCR beta chain variable (Vp) domain comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to residues 1-136 of SEQ ID NO: 92;v)a) a TCR alpha chain variable (Va) domain comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to residues 1-135 of SEQ ID NO: 93; andb) a TCR beta chain sequence comprising i) an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 92 or ii) an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 92, except with the following five substitutions: E153K, S157A, F268I, V271A, and Q274H; orvi)2023204645   23 Aug 2026a) a TCR alpha chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 93; and b) a TCR beta chain variable (Vp) domain comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to residues 1-136 of SEQ ID NO: 92.

20. The method of claim 18 or 19, wherein the binding protein comprises: i)a) a TCR alpha chain sequence comprising the sequence of SEQ ID NO: 93; and b) a TCR beta chain sequence comprising the sequence of SEQ ID NO: 92; or ii)a) a TCR alpha chain sequence comprising the sequence of SEQ ID NO: 93; and b) a TCR beta chain sequence comprising the sequence of SEQ ID NO: 92, except with the following five substitutions: E153K, S157A, F268I, V271A, and Q274H;iii)a) a TCR alpha chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 93; andb) a TCR beta chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 92; or iv)a) a TCR alpha chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 93; and b) a TCR beta chain sequence comprising an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the sequence of SEQ ID NO: 92, except with the following five substitutions: E153K, S157A, F268I, V271A, and Q274H.2023204645   23 Aug 202621. The method of any one of claims 18-20, wherein 1) the TCR alpha chain or TCR Va domain is encoded by a TRAV38-2DV8 and TRAJ11 gene and / or 2) TCR beta chain or TCR Vp domain is encoded by a TRBV30 and TRBJ2-3 gene.

22. The method of any one of claims 18-21, wherein:a) the cell is an allogeneic cell, syngeneic cell, or autologous cell;b) the cell is genetically modified;c) the cell comprises a chromosomal gene knockout of a TCR gene, an HLA gene, or both a TCR gene and an HLA gene;d) the cell comprises a knockout of an HLA gene selected from an al macroglobulin gene, a2 macroglobulin gene, a3 macroglobulin gene, 01 microglobulin gene, 02 microglobulin gene, and a combination thereof;e) the cell comprises a knockout of a TCR gene selected from a TCR a variable region gene, TCR 0 variable region gene, TCR constant region gene, and combinations thereof;f) the cell expresses CD8a and / or CD8p,optionally wherein the CD8a and / or CD8p is fused to a CD34 enrichment tag, optionally wherein cells are enriched using the CD34 enrichment tag;g) the cell is a hematopoietic progenitor cell, peripheral blood mononuclear cell (PBMC), cord blood cell, or immune cell;h) the immune cell is a cytotoxic lymphocyte, cytotoxic lymphocyte precursor cell, cytotoxic lymphocyte progenitor cell, cytotoxic lymphocyte stem cell, CD4+ T cell, CD8+ T cell, CD4 / CD8 double negative T cell, gamma delta (y§) T cell, natural killer (NK) cell, NK-T cell, dendritic cell, or combination thereof;i) the T cell is a naive T cell, central memory T cell, effector memory T cell, or combination thereof;j) the T cell is a primary T cell or a cell of a T cell line;k) the T cell does not express or has a lower surface expression of an endogenous TCR;l) the cell is capable of producing a cytokine or a cytotoxic molecule when contacted with a target cell that comprises a peptide-MHC (pMHC) complex comprising the HA-2 peptide epitope in the context of an MHC molecule;2023204645   23 Aug 2026m) the cytokine is TNF-a, IL-2, and / or IFN-y;n) the cytotoxic molecule is perforins and / or granzymes, optionally wherein the cytotoxic molecule is granzyme B;o) the cell is capable of producing a higher level of cytokine or a cytotoxic molecule when contacted with a target cell with a heterozygous expression of HA-2, optionally wherein the cell is capable of producing an at least 1.05-fold higher level of cytokine or a cytotoxic molecule;p) the host cell is capable of killing a target cell that comprises a peptide-MHC (pMHC) complex comprising an HA-2 peptide epitope in the context of an MHC molecule;q) the host cell is capable of killing a higher number of target cells when contacted with target cells with a heterozygous expression of HA-2;r) the host cell is capable of killing an at least 1.05-fold higher number of target cells;s) the HA-2 immunogenic peptide comprises the amino acid sequence YIGEVLVSV or YIGEVLVSM;t) the MHC molecule is an MHC class I molecule;u) the MHC molecule comprises an MHC alpha chain that is an HLA serotype HLA-A*02;v) the HLA allele is selected from the group consisting of HLA-A*02:01, HLA-A*02:02, HLA-A*02:03, HLA-A*02:05, HLA-A*02:06, and HLA-A*02:07 allele; and / orw) the target cell is a non-malignant cell or a hyperproliferating cell expressing the HA-2 antigen in the subject.

23. The method of any one of claims 18-22, wherein the composition:a) further comprises a pharmaceutically acceptable carrier;b) induces an immune response against the non-malignant cells or the hyperproliferating cells expressing the HA-2 antigen in the subject; and / orc) induces an antigen-specific T cell immune response against the non-malignant cells or the hyperproliferating cells expressing the HA-2 antigen in the subject, optionally wherein the antigen-specific T cell immune response comprises at least one of a CD4+ helper T lymphocyte (Th) response and a CD8+ cytotoxic T lymphocyte (CTL) response.

24. The method of any one of claims 6-23, wherein:2023204645   23 Aug 2026a) the hyperproliferative disorder comprises a hematological malignancy;b) the hematological malignancy comprises a leukemia, a lymphoma, a myelodysplastic disorder, a myeloproliferative neoplasm, or a myeloma;c) the hematological malignancy comprises a leukemia, optionally wherein the leukemia is selected from acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), mixed phenotype acute leukemia (MPAL), chronic myeloid leukemia (CML), B cell prolymphocytic leukemia, hairy cell leukemia, or chronic lymphocytic leukemia (CLL);d) the hematological malignancy comprises a lymphoma, optionally wherein the lymphoma is selected from Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), a central nervous system lymphoma, small lymphocytic lymphoma (SLL), CD37+ dendritic cell lymphoma, lymphoplasmacytic lymphoma, splenic marginal zone lymphoma, extra-nodal marginal zone B-cell lymphoma of mucosa-associated (MALT) lymphoid tissue, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, mediastinal (thymic) large B-cell lymphoma, precursor B-lymphoblastic lymphoma, immunoblastic large cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, or Burkitt's lymphoma;e) the hematological malignancy comprises a myelodysplastic disorder (MDS), optionally wherein the MDS is selected from refractory cytopenia with unilineage dysplasia (refractory anemia, refractory neutropenia, and refractory thrombocytopenia), refractory anemia with ring sideroblasts (RARS), refractory anemia with ring sideroblasts - thrombocytosis (RARS-t), refractory cytopenia with multilineage dysplasia (RCMD), refractory cytopenia with multilineage dysplasia and ring sideroblasts (RCMD-RS), refractory anemia with excess blasts (RAEB), myelodysplasia unclassifiable, refractory cytopenia of childhood, or MDS with isolated del(5q).

25. The method of any one of claims 6-23, wherein:a) the non-malignant disorder is an immune deficiency disorder, optionally wherein the immune deficiency disorder is selected from the group consisting of severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, Omenn syndrome, X-linked lymphoproliferative syndrome, chronic granulomatous disease, leukocyte adhesion deficiency, DiGeorge syndrome, and indications for hematopoietic stem cell transplantation (HCT);2023204645   23 Aug 2026b) the non-malignant disorder is a non-malignant hematology, optionally wherein the non-malignant hematology disorder is selected from the group consisting of as sickle cell anemia, thalassemia, aplastic anemia, hemophagocytic lymphohistiocytosis (HLH), severe aplastic anemia, marrow failure syndromes, Fanconi anemia, Diamond-Blackfan anemia, and Shwachman Diamond syndrome; orc) the non-malignant disorder is an autoimmune disorder, optionally wherein the autoimmune disorder is systemic sclerosis or multiple sclerosis.

26. The method of any one of claims 18-25, wherein:a) the subject is receiving or previously received a hematopoietic cell transplant (HCT), optionally wherein the HCT comprises cells that do not express HA-2 antigen, are not recognized by the binding protein, are not of serotype HLA-A*02, and / or do not express an HLA-A*02:01 allele, optionally wherein the HCT comprises a donor hematopoietic cell comprising a chromosomal knockout of a gene that encodes an HLA component, a chromosomal knockout of a gene that encodes a TCR component, or both;b) the subject had previously received lymphodepleting chemotherapy, optionally wherein the lymphodepleting chemotherapy comprised cyclophosphamide, fludarabine, antithymocyte globulin, or a combination thereof;c) the method further comprises administering at least one additional treatment for the non-malignant disorder, the hyperproliferative disorder or the relapse of a hyperproliferative disorder to the subject; and / ord) the at least one additional treatment for the non-malignant disorder, the hyperproliferative disorder or the relapse of a hyperproliferative disorder is administered concurrently or sequentially with the composition.

27. The method of any one of claims 5-26, wherein the subject is an animal model of a disorder characterized by HA-2 expression and / or the mammal, optionally wherein the mammal is a human, a primate, or a rodent.

28. The method of any one of claims 1-27, wherein:a) the binding protein is chimeric, humanized, or human;2023204645   23 Aug 2026b) the binding protein is a TCR, an antigen-binding fragment of a TCR, a single chain TCR (scTCR), a chimeric antigen receptor (CAR), or a fusion protein comprising a TCR and an effector domain, optionally wherein the binding domain comprises a transmembrane domain and an effector domain that is intracellular;c) the TCR alpha chain and the TCR beta chain are covalently linked, optionally wherein the TCR alpha chain and the TCR beta chain are covalently linked through a linker peptide;d) the TCR alpha chain and / or the TCR beta chain are covalently linked to a moiety, optionally wherein the covalently linked moiety comprises an affinity tag or a label, optionally wherein the affinity tag is selected from the group consisting of CD34 enrichment tag, Glutathione-S-Transferase (GST), calmodulin binding protein (CBP), protein C tag, Myc tag, HaloTag, HA tag, Flag tag, His tag, biotin tag, and V5 tag, and / or wherein the label is a fluorescent protein;e) the covalently linked moiety is selected from the group consisting of an inflammatory agent, cytokine, toxin, cytotoxic molecule, radioactive isotope, or antibody or antigen-binding fragment thereof;f) the binding protein binds to the pMHC complex on a cell surface;g) the MHC is a MHC multimer, optionally wherein the MHC multimer is a tetramer;h) the MHC is a MHC class I molecule;i) the MHC comprises an MHC alpha chain that is an HLA serotype HLA-A*02;j) the HLA allele is selected from the group consisting of HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0205, HLAA* 0206, and HLA-A*0207 allele, optionally wherein the HLA allele is HLA-A*0201;k) binding of the binding protein to the HA-1 peptide-MHC (pMHC) complex elicits an immune response, optionally wherein the immune response is a T cell response;l) the T cell response is selected from the group consisting of T cell expansion, cytokine release, and / or cytotoxic killing;m) the binding protein is capable of specifically and / or selectively binding to the HA-2 immunogenic peptide-MHC (pMHC) complex with a Kd less than or equal to about 1x10-4 M.

29. The method of any one of claims 1-28, wherein the binding protein is a TCR.2023204645   23 Aug 202630. The method of any one of claims 1-29, wherein the HLA allele is HLA-A*0201.

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