Humanized Anti-tcrbv9 antibodies

Abstract

Aspects of the application provide anti-TCRβV9 antibodies, polypeptides, and methods of using the same.

Description

HUMANIZED ANTI-TCRBV9 ANTIBODIESRELATED APPLICATIONS

[0001] This application claims benefit under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 63 / 756,551, filed February 10, 2025, entitled “Humanized Anti-TCRBV9 Antibodies”, the entire contents of which are incorporated herein by reference.REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[0002] The contents of the electronic sequence listing (H107670004WO00-SEQ-CNS.xml; Size: 1,025,077 bytes; and Date of Creation: February 3, 2026) are herein incorporated by reference in their entirety.BACKGROUND

[0003] T cell receptor beta variable 9 (TCR0V9) is a variable region of the beta (0) chain of the T cell receptor (TCR), encoded by the TCRfiV9 gene. TCR0V9 has been associated with some autoimmune conditions, including ankylosing spondylitis, celiac disease, inflammatory bowel disease, psoriatic arthritis, multiple sclerosis, and others.SUMMARY

[0004] Aspects of the disclosure provide polypeptides, which in some embodiments, have one or more improved properties relative to a polypeptide consisting of the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2 (e.g., reduced polyreactivity and / or reduced immunogenicity). In some embodiments, a polypeptide disclosed herein can be used for screening (e.g., screening for beneficial properties, such as binding). In some embodiments, a polypeptide disclosed herein can be used for producing a research tool (e.g., as a tool for assessing a cellular response to the polypeptide). In some embodiments, a polypeptide disclosed herein can be used for manufacturing a product of interest (e.g., manufacturing a therapeutic, such as a TCR0V9 targeting molecule).

[0005] Also provided herein are targeting molecules (e.g., antibodies) that specifically recognize and bind TCR0V9, which in some embodiments, have one or more improved properties relative to a previously disclosed anti-TCR0V9 antibody (e.g., improved binding affinity, reduced polyreactivity, and / or reduced immunogenicity). For example, in one aspect, the disclosure features an isolated antibody or antigen-binding fragment thereof that binds to TCR0V9 (e.g., human TCR0V9). In some embodiments, a TCR0V9 targeting molecule can 7107489be used to deplete TCRpV9-positive T cells. In some embodiments, a TCRPV9 targeting molecule can be used to neutralize TCRpV9-positive T cells. In some embodiments, a TCRPV9 targeting molecule can be used to identify TCRpV9-positive T cells (e.g., in a patient sample). TCRPV9 targeting molecules provided herein are useful for treating autoimmune diseases associated with TCRPV9 expression (e.g., ankylosing spondylitis, celiac disease, inflammatory bowel disease, psoriatic arthritis, multiple sclerosis, etc.).

[0006] Accordingly, in some embodiments, the disclosure provides a polypeptide comprising an amino acid sequence having at least 70% identity with the amino acid sequence of SEQ ID NO: 1, wherein the amino acid sequence has one or more alterations relative to the amino acid sequence of SEQ ID NO: 1. In some embodiments, the amino acid sequence comprises, relative to the amino acid sequence of SEQ ID NO: 1, one or more of the alterations provided in Table 1. In some embodiments, the polypeptide comprises a consensus sequence of SEQ ID NO: 1034 (X^X125), wherein each X is as provided for in Table 2.

[0007] In some aspects, the disclosure provides a polypeptide comprising an amino acid sequence have at least 80% identity with an amino acid sequence provided in Table 3. In some embodiments, the polypeptide is less immunogenic in humans relative to a polypeptide consisting of the amino acid sequence of SEQ ID NO: 1.

[0008] In some aspects, the disclosure provides a polypeptide comprising an amino acid sequence having at least 70% identity with the amino acid sequence of SEQ ID NO: 2, wherein the amino acid sequence has one or more alterations relative to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the amino acid sequence comprises, relative to the amino acid sequence of SEQ ID NO: 2, one or more of the alterations provided in Table 4. In some embodiments, the polypeptide comprises a consensus sequence of SEQ ID NO: 1035 (X^X107), wherein each X is as provided for in Table 5.

[0009] In some aspects, the disclosure provides a polypeptide comprising an amino acid sequence have at least 80% identity with an amino acid sequence provided in Table 6. In some embodiments, the polypeptide is less immunogenic in humans relative to a polypeptide consisting of the amino acid sequence of SEQ ID NO: 2.

[0010] In some embodiments, the disclosure provides a polynucleotide comprising a nucleotide sequence encoding a polypeptide provided herein. In some embodiments, the disclosure provides an expression vector comprising a nucleotide sequence encoding a polypeptide provided herein.

[0011] In some embodiments, the disclosure provides a cell comprising a polypeptide, a 7107489polynucleotide, or an expression vector provided herein.

[0012] In some embodiments, the disclosure provides a cell comprising one or more polynucleotides collectively comprising a first nucleotide sequence encoding a first polypeptide provided herein and a second nucleotide sequence encoding a second polypeptide provided herein. In some embodiments, the cell expresses a first polypeptide, second polypeptide pair provided in Table 7.

[0013] In some embodiments, the disclosure provides a method of producing a polypeptide, the method comprising: (i) culturing a cell provided herein under conditions suitable for expression of the polypeptide(s) by the cell; and (ii) harvesting the polypeptide(s). In some embodiments, the method further comprises (iii) purifying the polypeptide(s).

[0014] In some aspects, the disclosure provides a TCR[3V9 targeting molecule comprising an antibody that specifically binds to TCR[3V9, wherein the antibody comprises a heavy chain variable domain comprising: a CDR1 having the amino acid sequence of a CDR1 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with a CDR1 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3; a CDR2 having the amino acid sequence of a CDR2 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with a CDR2 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3; and a CDR3 having the amino acid sequence of a CDR3 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with a CDR3 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3.

[0015] In some embodiments, the CDRs of the heavy chain variable domain are determined according to Kabat. In some embodiments, the CDRs of the heavy chain variable domain are determined according to Chothia. In some embodiments, the CDRs of the heavy chain variable domain are determined according to IMGT. In some embodiments, the CDRs of the heavy chain variable domain are determined according to AbM. In some embodiments, the CDRs of the heavy chain variable domain are determined according to Contact.

[0016] In some aspects, the disclosure provides a TCR[3V9 targeting molecule comprising an antibody that specifically binds to TCR[3V9, wherein the antibody comprises a heavy chain variable domain comprising: a CDR1 having the amino acid sequence of DYLVH (SEQ ID NO: 3) or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with the 7107489amino acid sequence of SEQ ID NO: 3; a CDR2 having the amino acid sequence of WINTYTGTPTYADDFEG (SEQ ID NO: 4) or an amino acid sequence having 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 4; and a CDR3 having the amino acid sequence of SWRRGLRGIGFDY (SEQ ID NO: 5) or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 5, wherein the CDRs are determined according to Kabat; and wherein the amino acid sequence of the heavy chain variable domain comprises one or more alterations relative to the amino acid sequence of SEQ ID NO: 1.

[0017] In some embodiments, the heavy chain variable domain has increased affinity to TCRPV9 relative to a heavy chain variable domain consisting of the amino acid sequence of SEQ ID NO: 1. In some embodiments, the heavy chain variable domain is less immunogenic in humans relative to a heavy chain variable domain consisting of the amino acid sequence of SEQ ID NO: 1. In some embodiments, the heavy chain variable domain does not comprise a CDR1, CDR2, and CDR3 of SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, respectively, wherein the CDRs are determined according to Kabat.

[0018] In some embodiments, wherein the heavy chain variable domain comprises: a CDR1 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 3, one or more of the CDR1 alterations provided in Table 8; a CDR2 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 4, one or more of the CDR2 alterations provided in Table 8; and / or a CDR3 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 5, one or more of the CDR3 alterations provided in Table 8; wherein the CDRs are determined according to Kabat.

[0019] In some embodiments, the heavy chain variable domain comprises: a CDR1 comprising an amino acid sequence provided for a CDR1 in Table 9; a CDR2 comprising an amino acid sequence provided for a CDR2 in Table 9; and / or a CDR3 comprising an amino acid sequence provided for a CDR3 in Table 9; wherein the CDRs are determined according to Kabat. In some embodiments, the heavy chain variable domain comprises a CDR1, CDR2, and CDR3 combination provided in Table 9, wherein the CDRs are determined according to Kabat.

[0020] In some embodiments, the heavy chain variable domain comprises: a FR1 having the amino acid sequence of a FR1 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR1 of a heavy chain variable domain comprising an amino acid 7107489sequence provided in Table 3; a FR2 having the amino acid sequence of a FR2 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR2 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3; a FR3 having the amino acid sequence of a FR3 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR3 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3; and / or a FR4 having the amino acid sequence of a FR4 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR4 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3.

[0021] In some embodiments, the FRs of the heavy chain variable domain are determined according to Kabat. In some embodiments, the FRs of the heavy chain variable domain are determined according to Chothia. In some embodiments, the FRs of the heavy chain variable domain are determined according to IMGT. In some embodiments, the FRs of the heavy chain variable domain are determined according to AbM. In some embodiments, the FRs of the heavy chain variable domain are determined according to Contact.

[0022] In some embodiments, the heavy chain variable domain comprises: a FR1 having the amino acid sequence of QVQLVQSGSELKKPGESVKVSCKASGYTFT (SEQ ID NO: 6) or an amino acid sequence having 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 6; a FR2 having the amino acid sequence of WVRQAPGQGLEWMG (SEQ ID NO: 7) or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 7; a FR3 having the amino acid sequence of RFVFSLDTSVSTANLQISSLKAEDTAVYFCAR (SEQ ID NO: 8) or an amino acid sequence having 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 8; and / or a FR4 having the amino acid sequence of WGQGTLVTVSS (SEQ ID NO: 9) or an amino acid sequence having 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 5; wherein the FRs are determined according to Kabat.

[0023] In some embodiments, the heavy chain variable domain does not comprise a FR1, FR2, FR3, and FR4 of SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9, respectively, wherein the FRs are determined according to Kabat.

[0024] In some embodiments, the heavy chain variable domain comprises: a FR17107489comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 6, one or more of the FR1 alterations provided in Table 10; a FR2 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 7, one or more of the FR2 alterations provided in Table 10; a FR3 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 8, one or more of the FR3 alterations provided in Table 10; and / or a FR4 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 9, one or more of the FR4 alterations provided in Table 10; wherein the FRs are determined according to Kabat.

[0025] In some embodiments, the heavy chain variable domain comprises: a FR1 comprising an amino acid sequence provided for a FR1 in Table 11; a FR2 comprising an amino acid sequence provided for a FR2 in Table 11; a FR3 comprising an amino acid sequence provided for a FR3 in Table 11; and / or a FR4 comprising an amino acid sequence provided for a FR4 in Table 11; wherein the FRs are determined according to Kabat.

[0026] In some embodiments, the heavy chain variable domain comprises a FR1, FR2, FR3, and FR4 combination provided in Table 11, wherein the FRs are determined according to Kabat. In some embodiments, the heavy chain variable domain comprises an amino acid sequence having at least 80% identity with an amino acid sequence provided in Table 3. In some embodiments, the heavy chain variable domain consists of an amino acid sequence an amino acid sequence provided in Table 3.

[0027] In some embodiments, a TCR[3V9 targeting molecule provided herein further comprises a light chain variable domain, wherein the light chain variable domain comprises: a CDR1 having the amino acid sequence of a CDR1 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with a CDR1 of a light chain variable domain comprising an amino acid sequence provided in Table 6; a CDR2 having the amino acid sequence of a CDR2 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with a CDR2 of a light chain variable domain comprising an amino acid sequence provided in Table 6; and a CDR3 having the amino acid sequence of a CDR3 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with a CDR3 of a light chain variable domain comprising an amino acid sequence provided in Table 6.

[0028] In some embodiments, the CDRs of the light chain variable domain are determined according to Kabat. In some embodiments, the CDRs of the light chain variable domain are 7107489determined according to Chothia. In some embodiments, the CDRs of the light chain variable domain are determined according to IMGT. In some embodiments, the CDRs of the light chain variable domain are determined according to AbM. In some embodiments, the CDRs of the light chain variable domain are determined according to Contact.

[0029] In some embodiments, the antibody that specifically binds to TCRPV9 further comprises a light chain variable domain, wherein the light chain variable domain comprises: a CDR1 having the amino acid sequence of KASKSINKYL (SEQ ID NO: 10) or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 10; a CDR2 having the amino acid sequence of DGSTLQS (SEQ ID NO: 11) or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 11; and a CDR3 having the amino acid sequence of QQHNEYPPT (SEQ ID NO: 12) or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 12, wherein the CDRs are determined according to Kabat.

[0030] In some embodiments, the amino acid sequence of the light chain variable domain comprises one or more alterations relative to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the light chain variable domain has increased affinity to TCR[3V9 relative to a light chain variable domain consisting of the amino acid sequence of SEQ ID NO: 2. In some embodiments, the light chain variable domain is less immunogenic in humans relative to a heavy chain variable domain consisting of the amino acid sequence of SEQ ID NO: 2.

[0031] In some embodiments, the light chain variable domain does not comprise a CDR1, CDR2, and CDR3 of SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12, respectively, wherein the CDRs are determined according to Kabat.

[0032] In some embodiments, the light chain variable domain comprises: a CDR1 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 10, one or more of the CDR1 alterations provided in Table 12; a CDR2 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 11, one or more of the CDR2 alterations provided in Table 12; and / or a CDR3 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 12, one or more of the CDR3 alterations provided in Table 12; wherein the CDRs are determined according to Kabat.

[0033] In some embodiments, the light chain variable domain comprises: a CDR1 comprising an amino acid sequence provided for a CDR1 in Table 13; a CDR2 comprising an amino acid sequence provided for a CDR2 in Table 13; and / or a CDR3 comprising an amino 7107489acid sequence provided for a CDR3 in Table 13; wherein the CDRs are determined according to Kabat. In some embodiments, the light chain variable domain comprises a CDR1, CDR2, and CDR3 combination provided in Table 13, wherein the CDRs are determined according to Kabat.

[0034] In some embodiments, the light chain variable domain comprises: a FR1 having the amino acid sequence of a FR1 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR1 of a light chain variable domain comprising an amino acid sequence provided in Table 6; a FR2 having the amino acid sequence of a FR2 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR2 of a light chain variable domain comprising an amino acid sequence provided in Table 6; a FR having the amino acid sequence of a FR3 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR3 of a light chain variable comprising an amino acid sequence domain provided in Table 6; and / or a FR4 having the amino acid sequence of a FR4 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR4 of a light chain variable domain comprising an amino acid sequence provided in Table 6.

[0035] In some embodiments, the FRs of the light chain variable domain are determined according to Kabat. In some embodiments, the FRs of the light chain variable domain are determined according to Chothia. In some embodiments, the FRs of the light chain variable domain are determined according to IMGT. In some embodiments, the FRs of the light chain variable domain are determined according to AbM. In some embodiments, the FRs of the light chain variable domain are determined according to Contact.

[0036] In some embodiments, the light chain variable domain comprises: a FR1 having the amino acid sequence of DIQMTQSPYSLSASVGDRVTITC (SEQ ID NO: 13) or an amino acid sequence having 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 13; a FR2 having the amino acid sequence of AWFQQKPGKPNKLLIY (SEQ ID NO: 14) or an amino acid sequence having 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 14; a FR3 having the amino acid sequence of GVPSRFSGSGSGTDFTLTISSLEPEDFATYYC (SEQ ID NO: 15) or an amino acid sequence having 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 15; and / or a FR4 7107489having the amino acid sequence of FGQGTKLEIK (SEQ ID NO: 16) or an amino acid sequence having 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 16; wherein the FRs are determined according to Kabat.

[0037] In some embodiments, the light chain variable domain does not comprise a FR1, FR2, FR3, and FR4 of SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, and SEQ ID NO: 16, respectively, wherein the FRs are determined according to Kabat.

[0038] In some embodiments, the light chain variable domain comprises: a FR1 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 13, one or more of the FR1 alterations provided in Table 14; a FR2 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 14, one or more of the FR2 alterations provided in Table 14; a FR3 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 15, one or more of the FR3 alterations provided in Table 14; and / or a FR4 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 16, one or more of the FR4 alterations provided in Table 14; wherein the FRs are determined according to Kabat.

[0039] In some embodiments, the light chain variable domain comprises: a FR1 comprising an amino acid sequence provided for a FR1 in Table 15; a FR2 comprising an amino acid sequence provided for a FR2 in Table 15; a FR3 comprising an amino acid sequence provided for a FR3 in Table 15; and / or a FR4 comprising an amino acid sequence provided for a FR4 in Table 15; wherein the FRs are determined according to Kabat.

[0040] In some embodiments, the light chain variable domain comprises a FR1, FR2, FR3, and FR4 combination provided in Table 15, wherein the FRs are determined according to Kabat. In some embodiments, the light chain variable domain comprises an amino acid sequence having at least 80% identity with an amino acid sequence provided in Table 6. In some embodiments, the light chain variable domain consists of an amino acid sequence an amino acid sequence provided in Table 6.

[0041] In some embodiments, the TCRPV9 targeting molecule comprises a heavy chain variable domain, light chain variable domain pair provided in Table 16.

[0042] In some embodiments, the disclosure provides a polynucleotide comprising or a combination of polynucleotides collectively comprising a nucleotide sequence encoding TCRPV9 targeting molecule provided herein. In some embodiments, the disclosure provides an expression vector comprising a nucleotide sequence encoding a TCRPV9 targeting molecule provided herein. In some embodiments, the disclosure provides a cell comprising a TCRPV9 targeting molecule, a polynucleotide or combination of polynucleotides, or an 7107489expression vector provided herein.

[0043] In some embodiments, the disclosure provides a method of producing a TCRPV9 targeting molecule, the method comprising: (i) culturing a cell provided herein under conditions suitable for expression of the TCRPV9 targeting molecule by the cell; and (ii) harvesting the TCRPV9 targeting molecule. In some embodiments, the method further comprises (iii) purifying the TCRPV9 targeting molecule.

[0044] In some embodiments, the disclosure provides a composition comprising a TCRPV9 targeting molecule, a polynucleotide or combination of polynucleotides, an expression vector, or a cell provided herein; and a pharmaceutically acceptable excipient.

[0045] In some embodiments, the disclosure provides a method of treating or preventing a disease or condition characterized by expression of T cell receptor beta variable 9 (TCRPV9) in a subject, the method comprising administering to the subject a TCRPV9 targeting molecule, a polynucleotide or a combination of polynucleotides, an expression vector, a cell, or a composition provided herein.

[0046] In some embodiments, the disclosure provides a method of treating or preventing a T cell-mediated autoimmune or autoinflammatory disease in a subject, the method comprising administering to the subject a TCRPV9 targeting molecule, a polynucleotide or a combination of polynucleotides, an expression vector, a cell, or a composition provided herein.

[0047] In some embodiments, the disease or condition characterized by expression of TCRPV9 is an autoimmune disease. In some embodiments, the autoimmune disease is ankylosing spondylitis, celiac disease, inflammatory bowel disease, psoriatic arthritis, or multiple sclerosis. In some embodiments, the autoimmune disease is ankylosing spondylitis.

[0048] In some embodiments, the disclosure provides a method of reducing the number of cells expressing T cell receptor beta variable 9 (TCRPV9) in a subject, the method comprising administering to the subject a TCRPV9 targeting molecule, a polynucleotide or a combination of polynucleotides, an expression vector, a cell, or a composition provided herein. In some embodiments, the TCRPV9 targeting molecule increases killing of cells expressing TCRPV9 relative to killing of cells expressing TCRPV9 prior to the administration. In some embodiments, the TCRPV9 targeting molecule reduces the level of TCRPV9 in the blood of the subject. In some embodiments, the TCRPV9 targeting molecule increases killing of cells expressing TCRPV9 relative to killing of cells expressing TCRPV9 prior to the administration.

[0049] In some embodiments, the disclosure provides a method for detecting T cell 7107489receptor beta variable 9 (TCR0V9) in a sample, the method comprising contacting a sample with a TCR0V9 targeting molecule provided herein and detecting the formation of a complex of the TCRPV9 targeting molecule with TCRPV9. In some embodiments, the disclosure provides a kit comprising one or more containers comprising a TCRPV9 targeting molecule, a polynucleotide or a combination of polynucleotides, an expression vector, a cell, or a composition provided herein.

[0050] The foregoing and other aspects, implementations, acts, functionalities, features and embodiments of the present teachings can be more fully understood from the following description in conjunction with the accompanying drawings.BRIEF DESCRIPTION OF THE DRAWINGS

[0051] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate certain embodiments, and together with the written description, serve to provide non-limiting examples of certain aspects of the compositions and methods disclosed herein.

[0052] FIG. 1 provides amino acid numbering - sequential numbering and Kabat, Chothia, AbM, Contact, and IMGT CDR numbering - for the reference polypeptide of SEQ ID NO: 1.

[0053] FIG. 2 provides amino acid numbering - sequential numbering and Kabat, Chothia, AbM, Contact, and IMGT CDR numbering - for the reference polypeptide of SEQ ID NO: 2.DETAILED DESCRIPTION

[0054] T cell receptor beta variable 9 (TCR0V9, also referred to as TRBV9) is a variable region of the beta (0) chain of the T cell receptor (TCR), encoded by the TCR / 3V9 gene. The TCR alpha (TCRa) and TCR beta (TCR0) chains confer unique antigen specificity to the TCR, allowing for a vast repertoire of TCRs capable of recognizing a diversity of antigens. However, some TCR motifs are associated with autoimmune diseases, as they contribute to the aberrant recognition of self-antigen and immune attack of host tissue. Without wishing to be bound by theory, TCR0V9 has been strongly associated with numerous autoimmune conditions, including ankylosing spondylitis, celiac disease, psoriatic arthritis, inflammatory bowel disease, multiple sclerosis, and acute anterior uveitis.

[0055] The present disclosure, at least in part, is based on the development of polypeptides comprising an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99%) identity to the amino acid7107489sequence of SEQ ID NO: 1 or SEQ ID NO: 2. An antibody comprising the polypeptides of SEQ ID NO: 1 and SEQ ID NO: 2 has previously been shown to bind to TCRPV9. See e.g., WO 2019 / 132738; WO 2020 / 139171; WO2020 / 139175; WO2023 / 146437; WO2024 / 039268. In some embodiments, a polypeptide disclosed herein has one or more improved properties relative to a polypeptide consisting of the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2 (e.g., reduced polyreactivity and / or reduced immunogenicity). In some embodiments, a polypeptide disclosed herein can be used for screening (e.g., screening for beneficial properties, such as binding). In some embodiments, a polypeptide disclosed herein can be used for producing a research tool (e.g., as a tool for assessing a cellular response to the polypeptide). In some embodiments, a polypeptide disclosed herein can be used for manufacturing a product of interest (e.g., manufacturing a therapeutic, such as a TCRPV9 targeting molecule).

[0056] The present disclosure is also based, at least in part, on the development of TCRPV9 targeting molecules, which showed high binding affinity and specificity to TCRPV9. Also provided are the use of the TCRPV9 targeting molecules in research, diagnostic / detection, and therapeutic applications. Moreover, the TCRPV9 targeting molecules provided herein have undergone humanization, leading to reduced immunogenicity upon administration to human subjects. The reduction of immunogenicity is an important aspect of therapeutics, especially those that aim to ameliorate or reduce host immune activity. In some embodiments, when administered to a subject, the TCRPV9 targeting molecules provided herein target, reduce, or eliminate autoreactive TCRpV9-positive T cells; treat or ameliorate an autoimmune disorder or disorders associated with TCRpV9-positive T cells; and / or reduce or eliminate symptoms of autoimmune disorders associated with TCRPV9-positive T cells.

[0057] The foregoing and other aspects, implementations, acts, functionalities, features and embodiments of the present teachings can be more fully understood from the following description in conjunction with the accompanying drawings.I. Definitions

[0058] Administering: “Administering” or “administration” means to provide an antibody or a composition thereof to a subject in a manner that is physiologically and / or pharmacologically useful (e.g., to treat a condition in the subject).

[0059] Affinity Matured Antibody: “Affinity Matured Antibody” refers to an antibody with one or more alterations in one or more CDRs, which result in an improvement in the7107489affinity (z.e. KD, kd or ka) of the antibody for a target antigen compared to a parent antibody, which does not possess the alteration(s). Exemplary affinity matured antibodies will have nanomolar or even picomolar affinities for the target antigen. A variety of procedures for producing affinity matured antibodies are known in the art, including the screening of a combinatory antibody library that has been prepared using bio-display. For example, Marks et al., BioTechnology, 10: 779-783 (1992) describes affinity maturation by VH and VL domain shuffling. Random mutagenesis of CDR and / or framework residues is described by Barbas etal., Proc. Nat. Acad. Sci. USA, 91: 3809-3813 (1994); Schier etal., Gene, 169: 147-155 (1995); Yelton et al., J. Immunol., 155: 1994-2004 (1995); Jackson et al., J.Immunol., 154(7): 3310-3319 (1995); and Hawkins et al, J. Mol. Biol., 226: 889-896 (1992). Selective mutation at selective mutagenesis positions and at contact or hypermutation positions with an activity-enhancing amino acid residue is described in U.S. Pat. No.6,914,128 Bl.

[0060] Antibody: “Antibody” refers to a polypeptide that includes at least one immunoglobulin variable domain or at least one site, e.g., paratope, that specifically binds to an antigen. In some embodiments, an antibody is a full-length antibody. In some embodiments, an antibody is a chimeric antibody. In some embodiments, an antibody is a humanized antibody. However, in some embodiments, an antibody is a Fab fragment, a F(ab')2 fragment, a Fv fragment or a scFv fragment. In some embodiments, an antibody is a single domain antibody (e.g., NANOBODY®) derived from a camelid antibody or a single domain antibody (e.g., NANOBODY®) derived from shark antibody. In some embodiments, an antibody is a diabody. In some embodiments, an antibody comprises a framework having a human germline sequence. In another embodiment, an antibody comprises a heavy chain constant domain selected from the group consisting of IgG, IgGl, IgG2, IgG2A, IgG2B, IgG2C, IgG3, IgG4, IgAl, IgA2, IgD, IgM, and IgE constant domains.

[0061] In some embodiments, an antibody comprises a heavy (H) chain variable region (abbreviated herein as VH), and / or a light (E) chain variable region (abbreviated herein as VL). In some embodiments, an antibody comprises a constant domain, e.g., an Fc region. An immunoglobulin constant domain refers to a heavy or light chain constant domain.Human IgG heavy chain and light chain constant domain amino acid sequences and their functional variations are known.

[0062] In some embodiments, the heavy chain of an antibody described herein can be an alpha (a), delta (A), epsilon (E), gamma (y) or mu (p) heavy chain. In some embodiments, the7107489heavy chain of an antibody described herein can comprise a human alpha (a), delta (A), epsilon (E), gamma (y) or mu (p) heavy chain. In a particular embodiment, an antibody described herein comprises a human gamma 1 CHI, CH2, and / or CH3 domain. In some embodiments, the amino acid sequence of the VH domain comprises the amino acid sequence of a human gamma (y) heavy chain constant region, such as any known in the art. Nonlimiting examples of human constant region sequences have been described in the art, e.g., see U.S. Pat. No. 5,693,780 and Kabat E A et al., (1991) supra. In some embodiments, the VH domain comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or at least 99% identical to any of the variable chain constant regions provided herein.

[0063] In some embodiments, an antibody is modified, e.g., modified via glycosylation, phosphorylation, sumoylation, and / or methylation. In some embodiments, an antibody is a glycosylated antibody, which is conjugated to one or more sugar or carbohydrate molecules. In some embodiments, the one or more sugar or carbohydrate molecule are conjugated to the antibody via N-glycosylation, O-glycosylation, C-glycosylation, glypiation (GPI anchor attachment), and / or phosphoglycosylation. In some embodiments, the one or more sugar or carbohydrate molecule are monosaccharides, disaccharides, oligosaccharides, or glycans. In some embodiments, the one or more sugar or carbohydrate molecule is a branched oligosaccharide or a branched glycan. In some embodiments, the one or more sugar or carbohydrate molecule includes a mannose unit, a glucose unit, an N-acetylglucosamine unit, or a phospholipid unit.

[0064] In some embodiments, an antibody is a construct that comprises a polypeptide comprising one or more antigen binding fragments of the disclosure linked to a linker polypeptide or an immunoglobulin constant domain. Linker polypeptides comprise two or more amino acid residues joined by peptide bonds and are used to link one or more antigen binding portions. Examples of linker polypeptides have been reported (see e.g., Holliger, P., et al. (1993) Proc. Natl. Acad. Sci. USA 90:6444-6448; Poljak, R. J., et al. (1994) Structure 2:1121-1123). Still further, an antibody may be part of a larger immunoadhesion molecule, formed by covalent or noncovalent association of the antibody or antibody portion with one or more other proteins or peptides. Examples of such immunoadhesion molecules include use of the streptavidin core region to make a tetrameric scFv molecule (Kipriyanov, S. M., et al. (1995) Human Antibodies and Hybridomas 6:93-101) and use of a cysteine residue, a marker7107489peptide and a C-terminal polyhistidine tag to make bivalent and biotinylated scFv molecules (Kipriyanov, S. M., et al. (1994) Mol. Immunol. 31:1047-1058).

[0065] Antigen-Binding Molecule: “Antigen-binding molecule” includes a molecule that binds to a target antigen (e.g., TCRPV9), and encompasses monoclonal antibodies, polyclonal antibodies, monospecific antibodies, and antibody fragments, and other formats provided they bind to the relevant target molecule(s).

[0066] About:4‘About,” used interchangeably with “approximately”, as applied to one or more values of interest, refers to a value that is similar to a stated reference value. In certain embodiments, the term “approximately” or “about” refers to a range of values that fall within 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value).

[0067] CDR: ‘ ‘CDR” refers to the complementarity determining region within antibody variable sequences. A typical antibody molecule comprises a heavy chain variable region (VH) and a light chain variable region (VL), which are usually involved in antigen binding. The VH and VL regions can be further subdivided into regions of hypervariability, also known as “complementarity determining regions” (“CDR”), interspersed with regions that are more conserved, which are known as “framework regions” (“FR”). Each VH and VL is typically composed of three CDRs and four FRs, arranged from amino-terminus to carboxyterminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.

[0068] The extent of the framework region and CDRs can be precisely identified using methodology known in the art, for example, by the Kabat definition, the IMGT definition, the Chothia definition, the AbM definition, and / or the Contact definition, all of which are well known in the art. See, e.g., Kabat, E.A., et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No.91-3242; IMGT®, the international ImMunoGeneTics information system® http: / / www.imgt.org, Lefranc, M.-P. et al., Nucleic Acids Res., 27:209-212 (1999); Ruiz, M. et al., Nucleic Acids Res., 28:219-221 (2000); Lefranc, M.-P., Nucleic Acids Res., 29:207-209 (2001); Lefranc, M.-P., Nucleic Acids Res., 31:307-310 (2003); Lefranc, M.-P. etal., In Silico Biol., 5, 0006 (2004) [[Epub]], 5:45-60 (2005); Lefranc, M.-P. etal., Nucleic Acids Res., 33:D593-597 (2005); Lefranc, M.-P. et al., Nucleic Acids Res., 37:D1006-1012 (2009); Lefranc, M.-P. et al., Nucleic Acids Res., 43:D413-422 (2015); Chothia et al., (1989) Nature 342:877; Chothia, C. et al. (1987) J. Mol. Biol. 196:901-917, Al-lazikani et al (1997) J.7107489Molec. Biol. 273:927-948; and Almagro, J. Mol. Recognit. 17:132-143 (2004); see also hgmp.mrc.ac.uk and bioinf.org.uk / abs.

[0069] A CDR can include a CDR defined by any method known in the art. Two antibodies having the same CDR means that the two antibodies have the same amino acid sequence of that CDR as determined by the same method, for example, the IMGT definition.

[0070] In some embodiments, there are three CDRs in each of the variable regions of a heavy chain and a light chain, which are designated CDR1, CDR2 and CDR3, for each of the variable regions. “CDR set” as used herein refers to a group of three CDRs that occur in a single variable region capable of binding the antigen. The exact boundaries of these CDRs have been defined differently according to different systems. The system described by Kabat (Kabat etal., Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987) and (1991)) not only provides an unambiguous residue numbering system applicable to any variable region of an antibody, but also provides precise residue boundaries defining the three CDRs. These CDRs may be referred to as Kabat CDRs. Subportions of CDRs may be designated as LI, L2 and L3 or Hl, H2 and H3 where the "L" and the “H” designates the light chain and the heavy chains regions, respectively. These regions may be referred to as Chothia CDRs, which have boundaries that overlap with Kabat CDRs. Other boundaries defining CDRs overlapping with the Kabat CDRs have been described by Padlan (FASEB J. 9:133-139 (1995)) and MacCallum (J Mol Biol 262(5):732-45 (1996)). Still other CDR boundary definitions may not strictly follow one of the above systems, but will nonetheless overlap with the Kabat CDRs, although they may be shortened or lengthened in light of prediction or experimental findings that particular residues or groups of residues or even entire CDRs do not significantly impact antigen binding. The methods used herein may utilize CDRs defined according to any of these systems, including, but not limited to, Kabat, Chothia, AbM, Contact, or IMGT defined CDRs.In certain embodiments, the CDRs of an antibody may have different amino acid sequences when different definition systems are used (e.g., the IMGT definition, the Kabat definition, the Chothia definition, the AbM definition, or the Contact definition). A definition system annotates each amino acid in a given antibody sequence (e.g., VH or VL sequence) with a number, and numbers corresponding to the heavy chain and light chain CDRs, are provided in FIG. 1 and FIG. 2. The CDRs listed in Tables 8, 9, 12, and 13 are defined in accordance with the Kabat definition. One skilled in the art is able to derive the CDR sequences using the different numbering systems, such as Kabat, Chothia, AbM, Contact, and IMGT, as shown in FIGs. 1-2, for the anti-TCRpV9 antibodies provided in Tables 8, 9, 12, and 13.7107489

[0071] CDR-grafted antibody: “CDR-grafted antibody” refers to antibodies which comprise heavy and light chain variable region sequences from one species but in which the sequences of one or more of the CDR regions of VH and / or VL are replaced with CDR sequences of another species, such as antibodies having murine heavy and light chain variable regions in which one or more of the murine CDRs (e.g., CDR3) has been replaced with human CDR sequences.

[0072] Chimeric antibody: “Chimeric antibody” refers to antibodies which comprise sequences from more than one species, such as antibodies having murine heavy and light chain variable regions linked to human constant regions.

[0073] Complementary: “Complementary” refers to the capacity for precise pairing between two nucleotides or two sets of nucleotides. “Complementary” is a term that characterizes an extent of hydrogen bond pairing that brings about binding between two nucleotides or two sets of nucleotides. For example, if a base at one position of an oligonucleotide is capable of hydrogen bonding with a base at the corresponding position of a target nucleic acid e.g., an mRNA), then the bases are considered to be complementary to each other at that position. Base pairings may include both canonical Watson-Crick base pairing and non-Watson-Crick base pairing (e.g., Wobble base pairing and Hoogsteen base pairing). For example, in some embodiments, for complementary base pairings, adenosine-type bases (A) are complementary to thymidine-type bases (T) or uracil-type bases (U), that cytosine-type bases (C) are complementary to guano sine-type bases (G), and that universal bases such as 3-nitropyrrole or 5-nitroindole can hybridize to and are considered complementary to any A, C, U, or T. Inosine (I) has also been considered in the art to be a universal base and is considered complementary to any A, C, U or T.

[0074] Conservative amino acid substitution: A “conservative amino acid substitution” refers to an amino acid substitution that does not alter the relative charge or size characteristics of the protein in which the amino acid substitution is made. Variants can be prepared according to methods for altering polypeptide sequence known to one of ordinary skill in the art such as are found in references which compile such methods, e.g. Molecular Cloning: A Laboratory Manual, J. Sambrook, et al., eds., Fourth Edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2012, or Current Protocols in Molecular Biology, F.M. Ausubel, et al., eds., John Wiley & Sons, Inc., New York. Conservative substitutions of amino acids include substitutions made amongst amino acids within the following groups: (a) M, I, L, V; (b) F, Y, W; (c) K, R, H; (d) A, G; (e) S, T; (f) Q, N; and (g) E, D.7107489

[0075] Cross-reactive: In the context of a targeting agent (e.g., antibody), the term “cross-reactive,” refers to a property of the agent being capable of specifically binding to more than one antigen of a similar type or class e.g., antigens of multiple homologs, paralogs, or orthologs) with similar affinity or avidity. For example, in some embodiments, an antibody that is cross-reactive against human and non-human primate antigens of a similar type or class (e.g., a human TCRPV9 and non-human primate TCRPV9) is capable of binding to the human antigen and non-human primate antigens with a similar affinity or avidity. In some embodiments, an antibody is cross-reactive against a human antigen and a rodent antigen of a similar type or class. In some embodiments, an antibody is cross-reactive against a rodent antigen and a non-human primate antigen of a similar type or class. In some embodiments, an antibody is cross-reactive against a human antigen, a non-human primate antigen, and a rodent antigen of a similar type or class.

[0076] Effective Amount: An “effective amount” includes the amount of each active agent (e.g., TCRPV9 targeting molecule, such as an anti-TCRpV9 antibody) required to confer therapeutic effect on the subject, either alone or in combination with one or more other active agents.

[0077] In some embodiments, a therapeutic effect is reduction in the level of TCRPV9-positive cells, e.g., in the blood / serum / plasma of a treated subject.

[0078] In some embodiments, a therapeutic effect is reduction in the number / portion of cells (e.g., T cells) encoding / comprising / expressing TCRPV9 and / or cells (e.g., T cells) encoding / comprising / expressing a peptide / polypeptide / polypeptide complex (e.g., an antigen binding molecule) comprising TCR[3V9, e.g., in the treated subject (e.g., in the peripheral blood of the treated subject).

[0079] Framework: ‘ ‘Framework” or “framework sequence” or “Framework region” (“FR”) refers to the remaining sequences of a variable region minus the CDRs. Because the exact definition of a CDR sequence can be determined by different systems, the meaning of a framework sequence is subject to correspondingly different interpretations. The six CDRs (CDR-L1, CDR-L2, and CDR-L3 of light chain and CDR-H1, CDR-H2, and CDR-H3 of heavy chain) also divide the framework regions on the light chain and the heavy chain into four sub-regions (FR1, FR2, FR3, and FR4) on each chain, in which CDR1 is positioned between FR1 and FR2, CDR2 between FR2 and FR3, and CDR3 between FR3 and FR4. Without specifying the particular sub-regions as FR1, FR2, FR3 or FR4, a framework region, as referred by others, represents the combined FRs within the variable region of a single, naturally occurring immunoglobulin chain. As used herein, a FR represents one of the four 7107489sub-regions, and FRs represents two or more of the four sub-regions constituting a framework region. Human heavy chain and light chain acceptor sequences are known in the art. In one embodiment, the acceptor sequences known in the art may be used in the antibodies disclosed herein.

[0080] Human antibody: “Human antibody” includes antibodies having variable and constant regions derived from human germline immunoglobulin sequences. The human antibodies of the disclosure may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example in the CDRs and in particular CDR3. However, the term “human antibody”, as used herein, is not intended to include antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences.

[0081] Humanized antibody: “Humanized antibody” refers to antibodies which comprise heavy and light chain variable region sequences from a non-human species (e.g., a mouse) but in which at least a portion of the VH and / or VL sequence has been altered to be more “human-like”, i.e., more similar to human germline variable sequences. One type of humanized antibody is a CDR-grafted antibody, in which human CDR sequences are introduced into non-human VH and VL sequences to replace the corresponding nonhuman CDR sequences. In one embodiment, humanized anti-TCR[3V9 antibodies and antigen binding portions are provided. Such antibodies may be generated by obtaining murine anti-TCRPV9 monoclonal antibodies using traditional hybridoma technology followed by humanization using in vitro genetic engineering, such as those disclosed in Kasaian et al., International Publication No. WO 2005 / 123126 A2.

[0082] Humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat, or rabbit having the desired specificity, affinity, and capacity. In some embodiments, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, the humanized antibody may comprise residues that are found neither in the recipient antibody nor in the imported CDR or framework sequences, but are included to further refine and optimize antibody performance. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human7107489immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region or domain (Fc), typically that of a human immunoglobulin. Antibodies may have Fc regions modified as described in WO 99 / 58572. Other forms of humanized antibodies have one or more CDRs (one, two, three, four, five, six) which are altered with respect to the original antibody, which are also termed one or more CDRs derived from one or more CDRs from the original antibody. Humanized antibodies may also involve affinity maturation.

[0083] In some embodiments, humanization is achieved by grafting the CDRs (e.g., as shown in Tables 9 and 13) into the human variable domains (e.g., IGKV1-NL1*O1 and IGHV1-3*O1 human variable domain). In some embodiments, the anti-TCRpV9 antibody of the present disclosure is a humanized variant comprising one or more amino acid substitutions (e.g., in the VH framework region) as compared with any one of the VHs listed in Table 3, and / or one or more amino acid substitutions (e.g., in the VL framework region) as compared with any one of the VLs listed in Table 6.

[0084] Isolated antibody: An “isolated antibody” refers to an antibody that is substantially free of other antibodies having different antigenic specificities (e.g., an isolated antibody that specifically binds TCR[3V9 is substantially free of antibodies that specifically bind antigens other than TCR[3V9). An isolated antibody that specifically binds TCR[3V9 may, however, have cross-reactivity to other antigens. Moreover, an isolated antibody may be substantially free of other cellular material and / or chemicals.

[0085] Kabat numbering: “Kabat numbering” refers to a system of numbering amino acid residues that are more variable (i.e., hypervariable) than other amino acid residues in the heavy and light chain variable regions of an antibody, or an antigen binding portion thereof (Kabat et al. (1971) Ann. NY Acad, Sci. 190:382-391 and, Kabat, E. A., et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242). For a heavy chain variable region, the hypervariable region ranges from amino acid positions 31 to 35 for CDR1, amino acid positions 50 to 65 for CDR2, and amino acid positions 95 to 102 for CDR3. For a light chain variable region, the hypervariable region ranges from amino acid positions 24 to 34 for CDR1, amino acid positions 50 to 56 for CDR2, and amino acid positions 89 to 97 for CDR3.

[0086] Recombinant antibody: “Recombinant antibody” includes all antibodies that are prepared, expressed, created or isolated by recombinant means, such as antibodies expressed using a recombinant expression vector transfected into a host cell (described in more details in this disclosure), including, for example, antibodies isolated from a recombinant,7107489combinatorial human antibody library (Hoogenboom H. R., (1997) TIB Tech. 15:62-70; Azzazy H., and Highsmith W. E., (2002) Clin. Biochem. 35:425-445; Gavilondo J. V, and Larrick J. W. (2002) BioTechniques 29:128-145; Hoogenboom H., and Chames P. (2000) Immunology Today 21:371-378), antibodies isolated from an animal (e.g., a mouse) that is transgenic for human immunoglobulin genes (see e.g., Taylor, L. D., et al. (1992) Nucl. Acids Res. 20:6287-6295; Kellermann S-A., and Green L. L. (2002) Current Opinion in Biotechnology 13:593-597; Little M. et al. (2000) Immunology Today 21:364-370) or antibodies prepared, expressed, created or isolated by any other means that involves splicing of human immunoglobulin gene sequences to other DNA sequences. In some embodiments, recombinant human antibodies are provided herein. In some embodiments, such recombinant human antibodies have variable and constant domains derived from human germline immunoglobulin sequences. In some embodiments, however, such recombinant human antibodies are subjected to in vitro mutagenesis (or, when an animal transgenic for human Ig sequences is used, in vivo somatic mutagenesis) and thus the amino acid sequence of a VH region and / or VL region of a recombinant antibody, while derived from and related to human germline VH and / or VL sequence, may not naturally exist within the human antibody germline repertoire in vivo. One embodiment of the disclosure provides fully human antibodies capable of binding human TCRPV9 which can be generated using techniques well known in the art, such as, but not limited to, using human Ig phage libraries such as those disclosed in Jermutus et al., International Publication No. WO 2005 / 007699.

[0087] Selective: “Selective” or “selectively” refers to the ability of a molecule to produce an effect (e.g., inhibit, antagonize, agonize, etc.) in relation to its target molecule compared to a reference molecule. For example, a molecule that selectively inhibits its target molecule means that this molecule is capable of inhibiting its target molecule with a degree that is distinguishable from a reference molecule in an inhibition assay or other inhibitory context. For example, with respect to an inhibitor, “selectively inhibits,” refers to the ability of the inhibitor to inhibit its target molecule with a degree that is distinguishable from a reference molecule that is not substantially inhibited in an inhibition assay, e.g., to an extent that permit selective inhibition of the target molecule, as described herein. Once the reaction is terminated, the signal produced by inhibiting the target molecule can be measured. The half maximal inhibitor concentration for the target molecule and the reference molecule can be calculated. In some embodiments, a molecule described herein selectively binds to a target molecule (e.g., TCRPV9). In some embodiments, a molecule described herein (e.g., an anti-TCRPV9 antibody) selectively inhibits the interaction between TCRPV9 and a self antigen.7107489

[0088] Specifically binds: “Specifically binds” refers to the ability of a molecule to bind to a binding partner with a degree of affinity or avidity that enables the molecule to be used to distinguish the binding partner from an appropriate control in a binding assay or other binding context. With respect to an antibody, “specifically binds”, refers to the ability of the antibody to bind to a specific antigen with a degree of affinity or avidity, compared with an appropriate reference antigen or antigens, which enables the antibody to be used to distinguish the specific antigen from others, as described herein. In some embodiments, an antibody (e.g., an anti-TCRpV9 antibody) specifically binds to a target (e.g., TCRPV9) if the antibody has a KD for binding the target of at least about 10’4M, 10’5M, 10’6M, 10’7M, 10’8M, 10’9M, IO10M, 1011M, 1012M, 1013M, or less. In some embodiments, an antibody specifically binds TCRPV9.

[0089] The ability of a given polypeptide to bind specifically to a given molecule can be determined by analysis according to methods known in the art, such as by ELISA, Surface Plasmon Resonance (SPR; see e.g., Hearty et al., Methods Mol Biol (2012) 907:411-442), BioLayer Interferometry (see e.g., Lad et al., (2015) J Biomol Screen 20(4): 498-507), flow cytometry, or by a radio-labelled antigen-binding assay (RIA) enzyme-linked immunosorbent assay. Through such analysis binding to a given molecule can be measured and quantified. In some embodiments, the binding is the response detected in a given assay.

[0090] In some embodiments, the extent of binding of an antibody described herein e.g., anti-TCRpV9 antibody) binds to a non-target molecule by less than about 10% of the binding of the antibody to the target molecule as measured, e.g., by ELISA, SPR, Bio-Layer Interferometry or by RIA.

[0091] Subject: “Subject” includes a mammal. In some embodiments, a subject is nonhuman primate, or rodent. In some embodiments, a subject is a human. In some embodiments, a subject is a patient, e.g., a human patient that has or is suspected of having a disease.

[0092] In some embodiments, the subject is a human patient who has or is suspected of having ankylosing spondylitis and / or one or more conditions arising as a result of ankylosing spondylitis. In some embodiments, the subject is a human patient who has or is suspected of having celiac disease and / or one or more conditions arising as a result of celiac disease. In some embodiments, the subject is a human patient who has or is suspected of having psoriatic arthritis and / or one or more conditions arising as a result of psoriatic arthritis. In some embodiments, the subject is a human patient who has or is suspected of having acute anterior uveitis and / or one or more conditions arising as a result of acute anterior uveitis. In some 7107489embodiments, the subject is a human patient who has or is suspected of having inflammatory bowel disease (e.g., Crohn’s disease or colitis) and / or one or more conditions arising as a result of inflammatory bowel disease. In some embodiments, the subject is a human patient who has or is suspected of having multiple sclerosis and / or one or more conditions arising as a result of multiple sclerosis.

[0093] TCR V9: T-cell receptor (TCR) BV9 (TCRPV9, also referred to as TRBV9) refers to a specific variable region (VP9 or VB9) of the P-chain of TCRs. T cells with P-chains containing VB9 are associated with some autoimmune conditions, including ankylosing spondylitis, celiac disease, inflammatory bowel disease, psoriatic arthritis, multiple sclerosis, and others. TCRPV9 is encoded in humans by the TCR / 3V9 gene. In some embodiments, TCRPV9 has the amino acid sequence of SEQ ID NO: 17 (UniProt: A0A0B4J1U6):MGFRLLCCVAFCLLGAGPVDSGVTQTPKHLITATGQRVTLRC SPRSGDLSVYWYQQSLDQGLQFLIHYYNGEERAKGNILERFS AQQFPDLHSELNLSSLELGDSALYFCASSV (SEQ ID NO :17 )

[0094] TCRPV9 expression has been identified as overrepresented in T cells isolated from individuals with autoimmune disorders, including but not limited to ankylosing spondylitis, celiac disease, psoriatic arthritis, acute anterior uveitis, and multiple sclerosis. Such diseases are driven by autoreactive cells, especially autoreactive T cells, and TCRPV9 may therefore contribute to their etiology and / or pathology.

[0095] Reference to “TCRPV9” includes human TCRPV9 and variants, isoforms or fragments thereof. In some embodiments, TCRPV9 comprises or consists of an amino acid sequence having at 70% or greater amino acid sequence identity, preferably one of 75%, 80%, 85%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO: 17. In some embodiments, TCRPV9 comprises or consists of the amino acid sequence of SEQ ID NO: 17.

[0096] TCRPV9 Targeting Molecule: “TCRPV9 targeting molecule” includes any molecule (e.g., protein or chemical entity) comprising a domain that can specifically bind to TCRPV9. In some embodiments, a TCRPV9 targeting molecule is a TCRPV9 targeting polypeptide. A TCRPV9 targeting polypeptide includes a polypeptide comprising a domain (e.g., antigen binding domain) that can specifically bind to TCRPV9. In some embodiments, a TCRPV9 targeting molecules comprises an antibody that can specifically bind to TCRPV9, such as any one or more of the anti-TCRpV9 antibodies provided herein. In some embodiments, a TCRPV9 targeting molecule (e.g., antibodies) is monospecific (e.g., binding only to one other molecule (e.g., protein))7107489

[0097] Treatment: “Treating” or “treatment” includes the application or administration of a composition including one or more active agents (e.g., TCRPV9 targeting molecules, such as anti-TCRpV9 antibodies) to a subject, who has a target disease or disorder, a symptom of the disease / disorder, or a predisposition toward the disease / disorder, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve, or affect the disorder, the symptom of the disease, or the predisposition toward the disease or disorder. Alleviating a target disease / disorder includes delaying or preventing the development or progression of the disease or reducing disease severity.II. Polypeptides and Related Polynucleotides, Expressing Cells and Methods of Use

[0098] The present disclosure, at least in part, is based on the development of polypeptides comprising an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99%) identity to the amino acid sequence of SEQ ID NO: 1 and / or SEQ ID NO: 2. In some embodiments, the disclosure provides a polypeptide comprising an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99%) identity to the amino acid sequence of SEQ ID NO: 1. In some embodiments, the disclosure provides a polypeptide comprising an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99%) identity to the amino acid sequence of SEQ ID NO: 2.

[0099] In some embodiments a polypeptide comprises an alteration (e.g., a substitution, an insertion, or a deletion) at a position corresponding to a reference polypeptide (e.g., a polypeptide consisting of the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2). A polypeptide having a “position corresponding to” a reference amino acid sequence (e.g., a reference sequence such as the amino acid sequence of SEQ ID NO: 1) refers to a particular amino acid in the polypeptide to the reference polypeptide (e.g., the polypeptide of SEQ ID NO: 1).[000100] A polypeptide comprising one or more alterations may be identified relative to a reference polypeptide sequence. In other words, the reference polypeptide sequence can be used as a standard for mapping differences between polypeptides comprising alterations. This mapping may be used to compare polypeptides comprising insertions or deletions that shift the location of a mutation relative to the reference polypeptide sequence. In some embodiments, determining a position of an altered polypeptide (i.e., a polypeptide comprising one or more alterations) corresponding to a reference polypeptide sequence comprises 7107489aligning the reference polypeptide sequence and the altered polypeptide sequence (e.g., using Clustal Omega as described in Madeira et al., Nucleic Acids Res. 2024 Jul;52(Wl) W521-W525. PMID: 38597606). In some embodiments, this is determined using a structural alignment (e.g., as described in Bittrich et al., Bioinformatics, Volume 40, Issue 6, June 2024, doi.org / 10.1093 / bioinformatics / btae370).A. Polypeptides Having One or More Alterations Relative to SEQ ID NO: 1[000101] In some embodiments, the disclosure provides a polypeptide comprising an amino acid sequence having at least 70% e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99%) identity to the amino acid sequence of SEQ ID NO: 1, wherein the amino acid sequence has one or more alterations relative to the amino acid sequence of SEQ ID NO: 1. In some embodiments, a polypeptide provided herein has, relative to SEQ ID NO: 1, one or more (two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, or ten or more) alterations. In some embodiments, a polypeptide provided herein has 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, or 37 alterations, relative to SEQ ID NO: 1.[000102] In some embodiments, a polypeptide provided herein has, relative to SEQ ID NO: 1, an alteration at 1 or more of (2 or more of, 3 or more of, 4 or more of, 5 or more of, 6 or more of, 7 or more of, 8 or more of, 9 or more of, or 10 or more of) the amino acid positions provided in Table 1 (e.g., at one or more positions corresponding to QI, V2, Q6, S9, E10, Lil, K12, K13, E16, S17, V18, K19, V20, K23, A24, G26, Y27, T28, F29, T30, D31, Y32, L33, V34, H35, W36, R38, Q43, G44, M48, G49, 151, N52, T53, Y54, T55, G56, T57, P58, T59, Y60, A61, D62, D63, F64, E65, G66, F68, V69, S71, T74, V76, T78, A79, N80, L81, Q82, 183, S84, S85, K87, A88, E89, A97, R98, S99, W100, R101, R102, G103, L104, R105, G106, 1107, G108, F109, D100, Y111, T116, or LI 17 of SEQ ID NO: 1). In some embodiments, an alteration is a conservative amino acid substitution.[000103] In some embodiments, a polypeptide provided herein has, relative to SEQ ID NO: 1, one or more of (e.g., 2 or more of, 3 or more of, 4 or more of, 5 or more of, 6 or more of, 7 or more of, 8 or more of, 9 or more of, 10 or more of, etc.) the alterations provided in Table 1. In some embodiments, a polypeptide provided herein has 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, or 37 alterations relative to SEQ ID NO: 1, e.g., as provided in Table 1. In some embodiments, a polypeptide provided herein has a combination of alterations relative to SEQ ID NO: 1,7107489wherein the combination of alterations is provided in Table 1.Table 1. Alterations and Alteration Combinations of Exemplary Polypeptides. Positions correspond to the sequential positions (1-122) ofSEQ ID NO: 1.71074897107489710748971074897107489710748971074897107489710748971074897107489[000104] In some embodiments, the disclosure provides a consensus sequence of a polypeptide having one or more alterations relative to the amino acid sequence of SEQ ID NO: 1, wherein each position in the consensus sequence is represented by XN, wherein N represents the position of the residue within the polypeptide. In some embodiments, an amino acid at position XNis selected from an amino acid at a position selected from Table 2. In some embodiments, a polypeptide comprises a sequence of SEQ ID NO: 1034 (X!-X125), wherein: X1is Q or E; X2is V or I; X3is Q; X4is L; X5is V; X6is Q or E; X7is S; X8is G; X9is S, A, or G; X10is E or G; X11is L or V; X12is K or V; X13is K or Q; X14is P; X15is G; X16is E, A, or G; X17is S or T; X18is V or L; X19is K or R; X20is V, I, or L; X21is S; X22is C; X23is K or A; X24is A or V; X25is S; X26is G, I, K, N, R, S, or Y; X27is Y or F; X28is T, K, or R; X29is F, I, K, N, R, S, or Y; X30is T, D, I, K, L N, R, S, V, or Y; X31is D, I, K, N, R, S, or Y; X32is Y, I, K, N, R, or S; X33is L, D, K, or R; X34is V, I, or M; X35is H, I, K, N, R, S, or Y; X36is W, F, or V; X37is V; X38is R or Q; X39is Q; X40is A; X41is P; X42is G; X43is Q or K; X44is G or R; X45is L; X46is E; X47is W; X48is M or V; X49is G or S; X50is W; X51is I, K, N, R, S, or Y; X52is N or D; X53is T, I, K, N, R, S, or Y; X54is Y, A, D, E, K, L, N, Q, R, or S; X55is T, I, K, N, R, S, or Y; X56is G, I, K, N, R, S, or Y; X57is T, Q, or V; X58is P, I, K, N, R, S, or Y; X59is T, A, D, F, G, H, N, S, W, or Y; X60is Y, I, K, N, R, or S; X61is A, D, E, H, N, Q, R, S, T, V, or Y; X62is D, A, E, K, or S; X63is A or absent (also denoted absent; X65is D, A, E, K, or S; X66is F, L, V, or Y; X67is E, K, Q, R, or, L, N, R, S, V, or Y; X69is R; X70is F or V; X71is V or T; X72is F; X73is S or T; X74is L; X75is D; X76is T or A; X77is S; X78is V or A; X79is S; X80is T or S; X81is A; X82is L or absent; X83is N or Y; X84is L or M; X85is Q or E; X86is I, L, or M; X87is S, N, or R; X88is S or R; X89is L; X90is K or R; X91is A, S, or T; X92is E or D; X93is D; X94is T; X95is A; X96is V; X97is Y; X98is F; X99is C; X100is A, H, I, K, N, R, S, or Y; X101is R, A, D, F, G, I, L, S, T, or V; X102is S, I, K, N, R, or Y; X103is W, D, E, F, H, N, R, or Y; X104is R, I, or S; X105is R or G; X106is G, I, K, N, R, S, or Y; X107is L, I, K, N, R, S, or Y; X108is R, D, E, N, or T; X109is G, A, D, E, H, M, N, Q, S, T, V, or Y; X110is I, A, D, E, F, H, K, L, M, N, Q, R, S, T, V, W, or Y; X111is G, I, K, N, R, S, or Y; X112is F, I, K, N, R, S, or Y; X113is D, I, K, N, R, S, or Y; X114is Y, A, F, H, I, R, T, or V; X115is W; X116is G; X117is Q; X118is G; X119is T or V; X120is L or F; X121is V; X122is T; X123is V; X124is S; and X125is S.Table 2. Consensus Polypeptide Sequence (X!-X125) (SEQ ID NO: 1034). An absence of an amino acid is shown as71074897107489"[000105] In some embodiments, the disclosure provides a polypeptide comprising an amino acid sequence at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence provide in Table 3, wherein the polypeptide has one or more alterations relative to the amino acid sequence of SEQ ID NO: 1. In some embodiments, the disclosure provides a polypeptide comprising an amino acid sequence having no more than amino acid alterations (e.g., no more than 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alterations) as compared to an amino acid sequence provided in Table 3. In some embodiments, a polypeptide comprises or consists of an amino acid sequence provided in Table 3.Table 3. Amino Acid Sequences of Exemplary Polypeptides7107489710748971074897107489710748971074897107489710748971074897107489710748971074897107489710748971074897107489[000106] In some embodiments, a polypeptide does not comprise the amino acid sequence of QIQLVQSGPELREPGESVKLSCKASGYTFTDYLVHWVKQAPGKGLKWMGWINTYT GTPTYADDFEGRFVFSLEASASTANLQISNLKNEDTATYFCARSWRRGLRGLGFDY WGQGVFVTVSS (SEQ ID NO: 1015).[000107] In some embodiments, a polypeptide does not comprise the amino acid sequence of QIQEVQSGPEEREPGESVKESCKASGYTFTDYEVHWVKQAPGKGEKWMGWINTYT GTPTYADDFEGRFVFSEEASASTANEQISNEKNEDTATYFCARSWRRGERGIGFDYW GQGVFVTVSS (SEQ ID NO: 1016).[000108] In some embodiments, a polypeptide does not comprise the amino acid sequence of QIQEVQSGPEEREPGESVKESCKASGYTFTDYEVHWVKQAPGKGEKWMGWINTYT GTPTYADDFEGRFVFSEEASASTANEQISNEKNEDTATYFCARSWRRGIRGEGFDYW GQGVFVTVSS (SEQ ID NO: 1017).[000109] In some embodiments, a polypeptide does not comprise the amino acid sequence of QIQEVQSGPEEREPGESVKESCKASGYTFTDYEVHWVKQAPGKGEKWMGWINTYT GTPTYADDFEGRFVFSEEASASTANEQISNEKNEDTATYFCARSWRRGIRGIGFDYW GQGVFVTVSS (SEQ ID NO: 1018).[000110] In some embodiments, a polypeptide does not comprise the amino acid sequence of QIQEVQSGPEEKEPGESVKISCKASGYTFTDYEVHWVKQAPGKGIKWMGWINTYTG TPTYADDFEGRFVFSIEASASTANEQISNIKNEDTATYFCARSWRRGERGEGFDY(SEQ ID NO: 1019).[000111] In some embodiments, a polypeptide does not comprise the amino acid sequence of QIQLVQSGPEIKEPGESVKISCKASGYTFTDYLVHWVKQAPGKGIKWMGWINTYTGT PTYADDFEGRFVFSIEASASTANLQISNIKNEDTATYFCARSWRRGLRGLGFDY (SEQ ID NO: 1020).[000112] In some embodiments, a polypeptide does not comprise the amino acid sequence of QVQLVQSGPELKKPGESVKVSCKASGYTFTDYLVHWVRQAPGKGLEWMGWINTYT7107489GTPTYADDFEGRFVFSLDTSASTANLQICSLKNEDTATYYCARSWRRGLRGIGFDYW GQGTLVTVSS (SEQ ID NO: 1021).[000113] In some embodiments, a polypeptide does not comprise the amino acid sequence of QLQLVQSGPELREPGESVKISCKASGYTFTDYIVHWVKQAPGKGLKWMGWINTYTG TPTYADDFEGRFVFSLEASASTANLQISNLKNEDTATYFCARSWRRGIRGIGFDYWG QGVMVTVSS (SEQ ID NO: 1022).[000114] In some embodiments, a polypeptide does not comprise the amino acid sequence of QLQLVQSGAEVKKPGASVKVSCKASGYTFTDYIVHWVRQAPGQGLEWMGWINTYT GTPTYADDFEGWVTMTLDASISTAYMELSRLRSDDTAVYYCARSWRRGIRGIGFDY WGQGTMVTVSS (SEQ ID NO: 1023).[000115] In some embodiments, a polypeptide does not comprise the amino acid sequence of QLQLVQSGAEVKKPGASVKVSCKASGYTFTDYIVHWVRQAPGQGLEWMGWINTYT GTPTYADDFEGRVTMTLDASTSTAYMELSSLRSEDTAVYYCARSWRRGIRGIGFDY WGQGTMVTVSS (SEQ ID NO: 1024).[000116] In some embodiments, a polypeptide does not comprise the amino acid sequence of QLQLVQSGAEVKKPGASVKVSCKASGYTFTDYIVHWVRQAPGQRLEWMGWINTYT GTPTYADDFEGRVTITLDASASTAYMELSSLRSEDMAVYYCARSWRRGIRGIGFDY WGQGTMVTVSS (SEQ ID NO: 1025).[000117] In some embodiments, a polypeptide does not comprise the amino acid sequence of QLQLVQSGAEVKKPGASVKVSCKASGYTFTDYIVHWVRQATGQGLEWMGWINTYT GTPTYADDFEGRVTMTLNASISTAYMELSSLRSEDTAVYYCARSWRRGIRGIGFDYW GQGTMVTVSS (SEQ ID NO: 1026).[000118] In some embodiments, a polypeptide does not comprise the combination of a first amino acid sequence of DYLVH (SEQ ID NO: 3); a second amino acid sequence of WINTYTGTPTYADDFEG (SEQ ID NO: 4); and third amino acid sequence of SWRRGLRGLGFDY (SEQ ID NO: 770).[000119] In some embodiments, a polypeptide does not comprise the combination of a first amino acid sequence of DYLVH (SEQ ID NO: 3); a second amino acid sequence of WINTYTGTPTYADDFEG (SEQ ID NO: 4); and third amino acid sequence of SWRRGLRGIGFDY (SEQ ID NO: 5).[000120] In some embodiments, a polypeptide does not comprise the combination of a first amino acid sequence of DYLVH (SEQ ID NO: 3); a second amino acid sequence of WINTYTGTPTYADDFEG (SEQ ID NO: 4); and third amino acid sequence of SWRRGIRGLGFDY (SEQ ID NO: 1027).7107489[000121] In some embodiments, a polypeptide does not comprise the combination of a first amino acid sequence of DYLVH (SEQ ID NO: 3); a second amino acid sequence of WINTYTGTPTYADDFEG (SEQ ID NO: 4); and third amino acid sequence of SWRRGIRGIGFDY (SEQ ID NO: 743).[000122] In some embodiments, a polypeptide does not comprise the combination of a first amino acid sequence of DYIVH (SEQ ID NO: 1028); a second amino acid sequence of WINTYTGTPTYADDFEG (SEQ ID NO: 4); and third amino acid sequence of SWRRGIRGIGFDY (SEQ ID NO: 743).B. Polypeptides Having One or More Alterations Relative to SEQ ID NO: 2[000123] In some embodiments, the disclosure provides a polypeptide comprising an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99%) identity to the amino acid sequence of SEQ ID NO: 2, wherein the amino acid sequence has one or more alterations relative to the amino acid sequence of SEQ ID NO: 2. In some embodiments, a polypeptide provided herein has, relative to SEQ ID NO: 2, one or more (two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, or ten or more) alterations. In some embodiments, a polypeptide provided herein has 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 alterations relative to SEQ ID NO: 2.[000124] In some embodiments, a polypeptide provided herein has, relative to SEQ ID NO: 2, an alteration at 1 or more of (e.g., 2 or more of, 3 or more of, 4 or more of, 5 or more of, 6 or more of, 7 or more of, 8 or more of, 9 or more of, or 10 or more of) the amino acid positions provided in Table 4 (e.g., at one or more positions corresponding to DI, 12, Q3, S7, Y9, S10, Lil, S12, A13, S14, V15, D17, R18, V19, T20, 121, T22, K24, A25, S26, K27, S28, 129, N30, K31, Y32, L33, A34, F36, Q37, K39, G41, K42, P43, N44, K45, L47, D50, G51, S52, T53, L54, Q55, S56, G57, V58, S60, S67, D70, L73, T74, S76, S77, L78, E79, P80, F83, A84, T85, Y87, Q89, Q90, H91, N92, E93, Y94, P95, P96, or T97 of SEQ ID NO: 2). In some embodiments, an alteration is a conservative amino acid substitution.[000125] In some embodiments, a polypeptide provided herein has, relative to SEQ ID NO: 2, one or more of (e.g., 2 or more of, 3 or more of, 4 or more of, 5 or more of, 6 or more of, 7 or more of, 8 or more of, 9 or more of, 10 or more of, etc.) the alterations provided in Table 4. In some embodiments, a polypeptide provided herein has, relative to SEQ ID NO: 1, 2, 3, 71074894, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 alterations relative to SEQ ID NO: 2, e.g., as provided in Table 4. In some embodiments, a polypeptide provided herein has a combination of alterations relative to SEQ ID NO: 2, wherein the combination of alterations is provided in Table 4.Table 4. Alterations and Alteration Combinations of Exemplary Polypeptides. Positions correspond to the sequential positions (1-107) of SEQ ID NO: 2.7107489[000126] In some embodiments, the disclosure provides a consensus sequence of a polypeptide having one or more alterations relative to the amino acid sequence of SEQ ID NO: 2, wherein each position in the consensus sequence is represented by XN, wherein N represents the position of the residue within the polypeptide. In some embodiments, an amino acid at position XNis selected from an amino acid at a position selected from Table 5. In some embodiments, a polypeptide comprises a sequence of SEQ ID NO: 1035 (X^X107), wherein: X1X8is P; X9i7107489K, R, S, or Y; X31is K, S, or Y; X32is Y or S; X33is L, A, M, or V; X34is A or S; X35is W; X36is F or Y; X37is Q or L; X38is Q; X39is K or R; X40is P; X41is G or D; X42is K, E, or Q; X43is P, A, or S; X44is N, A, or P; X45is K, I, Q, or R; X46is L; X47is L or I; X48is I; X49is Y; X50is D, N, or Q; X51is G, S, or Y; X52is S or Y; X53is T, S, or Y; X54is L, S, or Y; X55is Q, A, F, N, S, or Y; X56is S or Y; X57is G or S; X58is V or I; X59is P; X60is S, A, D, or P; X61is R; X62is F; X63is S; X64is G; X65is S; X66is G; X67is S or Y; X68is G; X69is T; X70is D or E; X71is F; X72is T; X73is L or F; X74is T or K; X75is I; X76is S or N; X77is S, N, or R; X78is E, I, or V; X79is E or Q; X80is P, A, or S; X81is E; X82is D; X83is F, A, or V; X84is A or G; X85is T, V, or Y; X86is Y; X87is Y or F; X88is C; X89is Q, A, or M; X90is Q, K, R, S, or Y; X91is H, K, R, S, or Y; X92is N, A, F, G, H, W, or Y; X93is E, K, R, S, or Y; X94is Y, E, E, M, or R; X95is P, K, R, S, or Y; X96is P, K, R, S, or Y; X97is T, K, R, S, or Y; X98is F; X" is G; X100is Q; X101is G; X102is T; X103is K; X104is L; X105is E; X106is I; and X107is K.Table 5. Consensus Polypeptide Sequence (X1-X107) (SEQ ID NO: 1035)"7107489[000127] In some embodiments, the disclosure provides a polypeptide comprising an amino acid sequence at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an comprising an amino acid sequence provided in Table 6, wherein the polypeptide has one or more alterations relative to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the disclosure provides a polypeptide comprising an amino acid sequence having no more than 30 amino acid alterations (e.g., no more than 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alterations) as compared to an amino acid sequence provided in Table 6. In some embodiments, a polypeptide comprises or consists of an amino acid sequence provided in Table 6.Table 6. Amino Acid Sequences of Exemplary Polypeptides7107489710748971074897107489[000128] In some embodiments, a polypeptide does not comprise the amino acid sequence of DVQMTQSPYNLAASPGESVSINCKASKSINKYLAWYQQKPGKPNKLLIYDGSTLQSG IPSRFSGSGSGTDFTLTIRGLEPEDFGLYYCQQHNEYPPTFGAGTKLELK (SEQ ID NO: 1029).[000129] In some embodiments, a polypeptide does not comprise the amino acid sequence of EVVMTQSPGTLSLSPGERATLSCKASKSINKYLAWYQQKPGQAPRLLIYDGSTLQSGI PDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQHNEYPPTFGQGTKLEIK (SEQ ID NO: 1030).[000130] In some embodiments, a polypeptide does not comprise the amino acid sequence of EVVMTQSPATLSLSPGERATLSCKASKSINKYLAWYQQKPGQAPRLLIYDGSTLQSGI PARFSGSGSGTDFTLTISSLEPEDFAVYYCQQHNEYPPTFGQGTKLEIK (SEQ ID NO: 1031).[000131] In some embodiments, a polypeptide does not comprise the amino acid sequence of DVQMTQSPSSLSASVGDRVTITCKASKSINKYLAWYQQKPGKAPKLLIYDGSTLQSG VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHNEYPPTFGQGTKLEIK (SEQ ID NO: 1032).[000132] In some embodiments, a polypeptide does not comprise the amino acid sequence of AVRMTQSPSSFSASTGDRVTITCKASKSINKYLAWYQQKPGKAPKLLIYDGSTLQSG VPSRFSGSGSGTDFTLTISCLQSEDFATYYCQQHNEYPPTFGQGTKLEIK (SEQ ID NO: 1033).[000133] In some embodiments, a polypeptide does not comprise the combination of a first amino acid sequence of KASKSINKYL (SEQ ID NO: 10); a second amino acid sequence of DGSTLQS (SEQ ID NO: 11); and third amino acid sequence of QQHNEYPPT (SEQ ID NO: 12).[000134] In some embodiments, a polypeptide comprises an amino acid sequence at least 80% identical (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) to the amino acid sequence of SEQ ID NO: 2. In some embodiments, a polypeptide comprises an amino acid sequence of SEQ ID NO: 2.[000135] Also within the scope of the present disclosure are functional variants of any of the exemplary polypeptides as disclosed herein. A functional variant may contain one or more7107489amino acid residue alterations as relative to a reference polypeptide (e.g., at a position corresponding to a position in a reference polypeptide).C. Polypeptide Pairs[000136] In some embodiments, the disclosure provides a polypeptide pair comprising a first polypeptide and a second polypeptide. In some embodiments, a polypeptide pair comprises a first polypeptide selected from Table 3 (or a first polypeptide having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% with a polypeptide selected from Table 3) and a second polypeptide selected from Table 6 (or a second polypeptide having at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% with a polypeptide selected from Table 6). In some embodiments, a polypeptide pair is as provided in Table 7.Table 7. Amino Acid Sequences of Exemplary Polypeptide Pairs710748971074897107489710748971074897107489[000137] In some embodiments, a polypeptide pair of the present disclosure comprises a first7107489polypeptide at least 80% {e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a polypeptide selected from Table 3 and a second polypeptide at least 80% {e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a polypeptide selected from Table 6. In some embodiments, a polypeptide pair is at least 80% e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a polypeptide pair selected from Table 7. In some embodiments, a polypeptide pair of the disclosure comprises a first polypeptide and a second polypeptide that collectively contains no more than 5 amino acid alterations {e.g., no more than 5, 4, 3, 2, or 1 amino acid alterations) as compared to a polypeptide pair provided in Table 7. In some embodiments, a polypeptide pair of the disclosure comprises a first polypeptide and a second polypeptide that are collectively at least 80% {e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a polypeptide pair provided in Table 7. “Collectively” means that the total number of amino acid alterations in both the first polypeptide and the second polypeptide is within the defined range.D. Polynucleotide Encoding a Polypeptide Disclosed Herein[000138] In some embodiments, the disclosure provides a polynucleotide encoding a polypeptide disclosed herein {e.g., a polypeptide of Table 3 and / or Table 6). “Polynucleotide” refers to a polymer of nucleotides and is used interchangeably herein with “nucleic acid” and “nucleic acid molecule”. In some embodiments, a polynucleotide of the disclosure encodes a first polypeptide {e.g., a first polypeptide provided in Table 7). In some embodiments, a polynucleotide encodes a second polypeptide {e.g., a second polypeptide provided in Table 7). In some embodiments, a polynucleotide encodes a first polypeptide and a second polypeptide {e.g., a first polypeptide and a second polypeptide provided in Table 7). In some embodiments, a polynucleotide encoding a first polypeptide and a second polypeptide further encodes a linker and / or a signal peptide {e.g., to direct localization or expression of the first polypeptide and / or the second polypeptide). Polynucleotides encoding polypeptides of the disclosure can comprise any suitable codon for a given amino acid (for example, in the case where the same amino acid can be encoded by multiple codons, such as leucine). A7107489polynucleotide encoding polypeptide of the disclosure can also further encode a marker (e.g., a fluorescent marker or reporter protein).E. Cells Expressing a Polypeptide Disclosed Herein[000139] In some embodiments, the disclosure provides a cell expressing a polypeptide disclosed herein (e.g., a polypeptide of Table 3 and / or Table 6). In some embodiments, a cell expresses a first polypeptide (e.g., a first polypeptide provided in Table 7). In some embodiments, a cell expresses a second polypeptide (e.g., a second polypeptide provided in Table 7). In some embodiments, a cell expresses a first polypeptide and a second polypeptide (e.g., a first polypeptide and a second polypeptide provided in Table 7). In some embodiments, a cell is transduced or transfected with a polynucleotide encoding a polypeptide provided herein (e.g., as described in Section 11(D) of the present disclosure).E. Methods of Use[000140] In some embodiments, a polypeptide of the present disclosure can be used for production a research tool. For example, a polypeptide can be used as a tool for assessing a cellular response to the polypeptide. In some embodiments, a cellular response to a polypeptide of the disclosure comprises a decrease of cellular function. In some embodiments, a cellular response to a polypeptide of the disclosure comprises initiation of cell death. In some embodiments, a polypeptide can be used to detect a particular cell or cell population, such as a cell that recognizes or responds to the polypeptide. In some embodiments, a polypeptide disclosed herein can be used for manufacturing a product of interest, such as a therapeutic. For example, a polypeptide of the disclosure can be used in the manufacturing of a TCR[3V9 targeting molecule. In some embodiments, a polypeptide of the disclosure can used in combination with another therapeutic (e.g., an antibody) to produce a new therapeutic or a new combination therapy.III. Anti-TCRpV9 Antibodies and Related Polynucleotides, Expressing Cells and Methods of Use[000141] Provided herein, in some aspects, are antibodies that bind to human TCR[3V9 with high specificity and affinity. In some embodiments, the anti-TCR[3V9 antibody described herein specifically binds to any extracellular epitope of a TCR[3V9 or an epitope that becomes exposed to an antibody.7107489[000142] In some embodiments, an anti-TCRpV9 antibody provided herein binds to T cell receptor (TCR). In some embodiments, an anti-TCRpV9 antibody binds to a TCR alpha chain (TCRa). In some embodiments, an anti-TCRpV9 antibody binds to a TCR beta chain (TCRP). In some embodiments, an anti-TCRpV9 antibody binds to a combination of TCRa and TCRP (TCRa / p). In some embodiments, anti-TCRpV9 antibodies provided herein bind to human TCRPV9. In some embodiments, the anti-TCRpV9 antibody described herein binds to an amino acid segment of a human TCRPV9. In some embodiments, an anti-TCRPV9 antibody described herein specifically binds to an epitope on human TCRPV9.[000143] In some embodiments, the anti-TCRpV9 antibody described herein may bind to a fragment of a human TCRPV9. The fragment of TCRPV9 may be between about 5 and about 114 amino acids, between about 10 and about 114 amino acids, between about 25 and about 100 amino acids, between about 50 and about 100 amino acids, between about 75 and about 100 amino acids, between about 85 and about 100 amino acids, or between about 95 and about 100 amino acids in length. The fragment may comprise a contiguous number of amino acids from TCRPV9.[000144] In some embodiments, an anti-TCRpV9 antibody provided herein is configured as a bispecific antibody (e.g., a bispecific antibody comprising one arm comprising an anti-TCRPV9 antibody provided herein and one arm comprising an antibody that specifically binds a second target). In some embodiments, an anti-TCRpV9 antibody is configured as a multispecific antibody (e.g., a multispecific antibody comprising one arm comprising an anti-TCRPV9 antibody provided herein and two or more arms comprising an antibody that specifically binds two or more additional targets).[000145] In some embodiments, an anti-TCRpV9 antibody is configured as a natural killer (NK) cell engager (e.g., a molecule that comprises an anti-TCRpV9 antibody provided herein and a second binding site that specifically binds an antigen expressed by an NK cell). In some embodiments, an anti-TCRpV9 antibody is configured as a T cell engager (e.g., a molecule that comprises an anti-TCRpV9 antibody provided herein and a second binding site that specifically binds an antigen expressed by a T cell). In some embodiments, an anti-TCRpV9 antibody is configured as a myeloid cell engager (e.g., a molecule that comprises an anti-TCRPV9 antibody provided herein and a second binding site that specifically binds an antigen expressed by a myeloid cell).[000146] In some embodiments, an anti-TCRpV9 antibody is configured as part of a chimeric antigen receptor (CAR) (e.g., in some embodiments, the antigen-binding domain of a CAR comprises an anti-TCRpV9 antibody provided herein).7107489[000147] In some embodiments, an anti-TCRpV9 antibody is configured as an antibody-drug conjugate (ADC). In some embodiments, an anti-TCRpV9 antibody is configured as an immunocytokine fusion.[000148] In some embodiments, an anti-TCRpV9 antibody is useful in cell therapy (e.g., ex vivo or in vivo cell therapy).[000149] In some embodiments, an anti-TCRpV9 antibody is encapsulated in a lipid nanoparticle (LNP). In some embodiments, an anti-TCRpV9 antibody is encapsulated in a LNP that further comprises an RNA molecule.[000150] In some embodiments, an anti-TCRpV9 antibody described herein binds a portion of human TCRPV9 comprising a sequence of SEQ ID NO: 17. In some embodiments, an anti-TCRpV9 antibody described herein is an affinity matured clone.[000151] In some embodiments, the anti-TCRpV9 antibodies described herein are affinity matured clones. In some embodiments, an anti-TCRpV9 antibody specifically binds a TCRPV9 (e.g., a human or non-human primate TCRPV9) with binding affinity (e.g., as indicated by KD) of at least about 10’4M, 10’5M, 10’6M, 10’7M, 10’8M, 10’9M, IO10M, 10’11M, 1012M, 1013M, or less. For example, the anti-TCRpV9 antibodies of the present disclosure can bind to a TCRPV9 protein (e.g., human TCRPV9) with an affinity between 5 pM and 500 nM, e.g., between 50 pM and 100 nM, e.g., between 500 pM and 50 nM. The disclosure also includes antibodies that compete with any of the antibodies described herein for binding to a TCRPV9 protein e.g., human TCRPV9) and that have an affinity of 100 nM or lower (e.g., 80 nM or lower, 50 nM or lower, 20 nM or lower, 10 nM or lower, 500 pM or lower, 50 pM or lower, or 5 pM or lower). The affinity and binding kinetics of the anti-TCRPV9 antibody can be tested using any suitable method including but not limited to biosensor technology (e.g., OCTET or BIACORE). In some embodiments, the anti-TCRpV9 antibodies described herein binds to TCRPV9 with a KD of sub-nanomolar range or submicromolar range.[000152] Binding affinity (or binding specificity) can be determined by a variety of methods including equilibrium dialysis, equilibrium binding, gel filtration, ELISA, surface plasmon resonance (SPR), fluorescent activated cell sorting (FACS) or spectroscopy (e.g., using a fluorescence assay). Exemplary conditions for evaluating binding affinity are in HBS-P buffer (10 mM HEPES pH7.4, 150 mM NaCl, 0.005% (v / v) surfactant P20) and PBS buffer (lOmM PO4-3, 137mM NaCl, and 2.7mM KC1). These techniques can be used to measure the concentration of bound proteins as a function of target protein concentration. The7107489concentration of bound protein ([[Bound]]) is generally related to the concentration of free target protein ([[Free]]) by the following equation:[[Bound]] = [[Free]] / (Kd+[[Free]])[000153] It is not always necessary to make an exact determination of KA, though, since sometimes it is sufficient to obtain a quantitative measurement of affinity, e.g., determined using a method such as ELISA or FACS analysis, is proportional to KA, and thus can be used for comparisons, such as determining whether a higher affinity is, e.g., 2-fold higher, to obtain a qualitative measurement of affinity, or to obtain an inference of affinity, e.g., by activity in a functional assay, e.g., an in vitro or in vivo assay.[000154] The heavy chain variable domain (VH) and light chain variable domain (VL), CDR sequences, framework sequences, and alterations and combinations thereof of exemplary anti-TCRpV9 antibodies are provided in Tables 8-16.A. Heavy Chain Variable Domains[000155] In some embodiments, an anti-TCR[3V9 antibody provided herein comprises a heavy chain variable domain having increased affinity to TCR[3V9 relative to a heavy chain variable domain consisting of the amino acid sequence of SEQ ID NO: 1.[000156] In some embodiments, the disclosure provides a TCR[3V9 targeting molecule comprising an antibody that specifically binds to TCR[3V9, wherein the antibody comprises a heavy chain variable domain comprising: a CDR1 having the amino acid sequence of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with a CDR1 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3; a CDR2 having the amino acid sequence of a CDR2 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 3, 2, or 1 amino acid alteration (s) with a CDR2 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3; and / or a CDR3 having the amino acid sequence of a CDR3 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with a CDR3 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3. In some embodiments, CDRs of a heavy chain variable domain are determined according to Kabat. In some embodiments, CDRs of a heavy chain variable domain are determined according to Chothia. In some embodiments, CDRs of a heavy chain variable domain are determined according to IMGT. In some embodiments, CDRs of a heavy chain variable domain are 7107489determined according to AbM. In some embodiments, CDRs of a heavy chain variable domain are determined according to Contact.[000157] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a heavy chain variable domain comprising: a CDR1 having the amino acid sequence of DYLVH (SEQ ID NO: 3) or an amino acid sequence having one or more amino acid alterations with the amino acid sequence of DYLVH (SEQ ID NO: 3); a CDR2 having the amino acid sequence of WINTYTGTPTYADDFEG (SEQ ID NO: 4) or an amino acid sequence having one or more amino acid alterations with the amino acid sequence of SEQ ID NO: 4; and a CDR3 having the amino acid sequence of SWRRGLRGIGFDY (SEQ ID NO: 5) or an amino acid sequence having one or more amino acid alterations with the amino acid sequence of SEQ ID NO: 5; and wherein the amino acid sequence of the heavy chain variable domain comprises one or more alterations relative to the amino acid sequence of SEQ ID NO: 1.[000158] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a heavy chain variable domain comprising a CDR1 having one or more (e.g., 2 or more or 3 or more) amino acid alterations with the amino acid sequence of DYLVH (SEQ ID NO: 3). In some embodiments, the CDR1 comprises 1, 2, or 3 amino acid alteration(s) with the amino acid sequence of DYLVH (SEQ ID NO: 3). In some embodiments, the CDR1 comprises an alteration at one or more of the CDR1 amino acid positions provided in Table 8 e.g., at one or more positions corresponding to D31, Y32, L33, V34, or H35 of SEQ ID NO: 1). In some embodiments, the CDR1 comprises 1, 2, or 3 of the alterations (CDR1 Alterations) provided in Table 8. In some embodiments, the CDR1 comprises a combination of alterations (CDR1 Combination Alterations) provided in Table 8.[000159] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a heavy chain variable domain comprising a CDR2 having one or more (two or more, three or more, four or more, five or more, six or more, seven or more, or eight or more) amino acid alterations with the amino acid sequence of WINTYTGTPTYADDFEG (SEQ ID NO: 4). In some embodiments, the CDR2 comprises 1, 2, 3, 4, 5, 6, 7, or 8 amino acid alteration(s) with the amino acid sequence of WINTYTGTPTYADDFEG (SEQ ID NO: 4). In some embodiments, the CDR2 comprises an alteration at one or more of the CDR2 amino acid positions provided in Table 8 (e.g., at one or more positions corresponding to 151, N52, T53, Y54, T55, G56, T57, P58, T59, Y60, A61, D62, D63, F64, E65, or G66 of SEQ ID NO: 1). In some embodiments, the CDR2 comprises 1, 2, 3, 4, 5, 6, 7, or 8 of the alterations (CDR2 Alterations) provided in Table 8. In some embodiments, the CDR2 comprises a combination 7107489of alterations (CDR2 Combination Alterations) provided in Table 8.[000160] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a heavy chain variable domain comprising a CDR3 having one or more (two or more, three or more, four or more, or five or more) amino acid alterations with the amino acid sequence of SWRRGLRGIGFDY (SEQ ID NO: 5). In some embodiments, the CDR3 comprises 1, 2, 3, 4, or 5 amino acid alteration(s) with the amino acid sequence of SWRRGLRGIGFDY (SEQ ID NO: 5). In some embodiments, the CDR3 comprises an alteration at one or more of the CDR3 amino acid positions provided in Table 8 (e.g., at one or more positions corresponding to S99, W100, R101, R102, G103, L104, R105, G106, 1107, G108, F109, F110, or Ylll of SEQ ID NO: 1). In some embodiments, the CDR3 comprises 1, 2, 3, 4, or 5 of the alterations (CDR3 Alterations) provided in Table 8. In some embodiments, the CDR3 comprises a combination of alterations (CDR3 Combination Alterations) provided in Table 8.[000161] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a heavy chain complementarity determining region 1 (HC CDR1), a HC CDR2, and a HC CDR3 collectively comprising one or more (two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, or ten or more) alterations as compared to: a HC CDR1 having the amino acid sequence of SEQ ID NO: 3; a HC CDR2 having the amino acid sequence of SEQ ID NO: 4; and a HC CDR3 having the amino acid sequence of SEQ ID NO: 5. In some embodiments, the one or more (two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, or ten or more) alterations are provided in Table 8. In some embodiments, an anti-TCRpV9 antibody provided herein comprises a HC CDR1, a HC CDR2, and HC CDR3 having a combination of alterations (CDR 1-3 Alteration Combination) provided in Table 8. Variable heavy domain CDRs referred to herein can be determined according to any CDR numbering convention (e.g., Kabat, Chothia, AbM, Contact, and IMGT, as shown in FIG. 1).Table 8. Alterations and Alteration Combinations of Exemplary Variable Heavy CDRs. Positions correspond to the sequential positions (1-122) of SEQ ID NO: 1. For corresponding Kabat, Chothia, AbM, Contact, and IMGT numbering, see FIG. 1.710748971074897107489[000162] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a HC CDR1 provided in Table 9. In some embodiments, an anti-TCRpV9 antibody comprises a HC CDR1 that has no more than 5 amino acid alterations (e.g., no more than 5, 4, 3, 2, or 1 amino acid alterations) as compared to a HC CDR1 provided in Table 9. In some embodiments, an anti-TCRpV9 antibody comprises a HC CDR1 that is at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a HC CDR1 provided in Table 9.[000163] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a HC CDR2 provided in Table 9. In some embodiments, an anti-TCRpV9 antibody comprises a HC CDR2 that has no more than 5 amino acid alterations (e.g., no more than 5, 4, 3, 2, or 1 amino acid alterations) as compared to a HC CDR2 provided in Table 9. In some embodiments, an anti-TCRpV9 antibody comprises a HC CDR2 that is at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a HC CDR2 provided in Table 9.[000164] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a HC CDR3 provided in Table 9. In some embodiments, an anti-TCRpV9 antibody comprises a HC CDR3 that has no more than 5 amino acid alterations (e.g., no more than 5, 4, 3, 2, or 1 amino acid alterations) as compared to a HC CDR3 provided in Table 9. In some embodiments, an anti-TCRpV9 antibody comprises a HC CDR3 that is at least 80% (e.g., at7107489least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a HC CDR3 provided in Table 9.[000165] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a HC CDR1, a HC CDR2, and a HC CDR3 combination provided in Table 9. In some embodiments, an anti-TCRpV9 antibody comprises a HC CDR1, a HC CDR2, and a HC CDR3 combination that collectively has no more than 5 amino acid alterations (e.g., no more than 5, 4, 3, 2, or 1 amino acid alterations) as compared to a HC CDR1, a HC CDR2, and a HC CDR3 combination provided in Table 9. In some embodiments, an anti-TCRpV9 antibody comprises a HC CDR1, a HC CDR2, and a HC CDR3 combination that is collectively at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a HC CDR1, a HC CDR2, and a HC CDR3 combination provided in Table 9.Table 9. Amino Acid Sequences of Exemplary Variable Heavy CDRs and CDR Combinations. CDRs are provided according to Kabat numbering.710748971074897107489710748971074897107489710748971074897107489[000166] In some embodiments, an anti-TCRpV9 antibody provided herein does not comprise a HC CDR1-3 combination of the antibody BL37.2. See e.g., WO 2020 / 010250 A2, Table 10A. In some embodiments, an anti-TCRpV9 antibody provided herein does not comprise a HC CDR1-3 combination of an antibody disclosed in WO 2019 / 132738 Al, WO 2020 / 139171 Al, WO 2020 / 139175 A2, WO 2023 / 146437 Al, or WO 2024 / 039268 Al.[000167] In some embodiments, an anti-TCRpV9 antibody provided herein does not comprise the combination of: a HC CDR1 consisting of the amino acid sequence of DYLVH (SEQ ID NO: 3); a HC CDR2 consisting of the amino acid sequence of WINTYTGTPTYADDFEG (SEQ ID NO: 4); and a HC CDR3 consisting of the amino acid7107489sequence of SWRRGLRGLGFDY (SEQ ID NO: 770), wherein the CDRs are determined according to Kabat numbering.[000168] In some embodiments, an anti-TCRpV9 antibody provided herein does not comprise the combination of: a HC CDR1 consisting of the amino acid sequence of DYLVH (SEQ ID NO: 3); a HC CDR2 consisting of the amino acid sequence of WINTYTGTPTYADDFEG (SEQ ID NO: 4); and a HC CDR3 consisting of the amino acid sequence of SWRRGLRGIGFDY (SEQ ID NO: 5), wherein the CDRs are determined according to Kabat numbering.[000169] In some embodiments, an anti-TCRpV9 antibody provided herein does not comprise the combination of: a HC CDR1 consisting of the amino acid sequence of DYLVH (SEQ ID NO: 3); a HC CDR2 consisting of the amino acid sequence of WINTYTGTPTYADDFEG (SEQ ID NO: 4); and a HC CDR3 consisting of the amino acid sequence of SWRRGIRGLGFDY (SEQ ID NO: 1027), wherein the CDRs are determined according to Kabat numbering.[000170] In some embodiments, an anti-TCRpV9 antibody provided herein does not comprise the combination of: a HC CDR1 consisting of the amino acid sequence of DYLVH (SEQ ID NO: 3); a HC CDR2 consisting of the amino acid sequence of WINTYTGTPTYADDFEG (SEQ ID NO: 4); and a HC CDR3 consisting of the amino acid sequence of SWRRGIRGIGFDY (SEQ ID NO: 743), wherein the CDRs are determined according to Kabat numbering.In some embodiments, an anti-TCRpV9 antibody provided herein does not comprise the combination of: a HC CDR1 consisting of the amino acid sequence of DYIVH (SEQ ID NO: 1028); a HC CDR2 consisting of the amino acid sequence of WINTYTGTPTYADDFEG (SEQ ID NO: 4); and a HC CDR3 consisting of the amino acid sequence of SWRRGIRGIGFDY (SEQ ID NO: 743), wherein the CDRs are determined according to Kabat numbering.[000171] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a heavy chain variable domain comprising: a FR1 having the amino acid sequence of QVQLVQSGSELKKPGESVKVSCKASGYTFT (SEQ ID NO: 6) or an amino acid sequence having one or more amino acid alterations with the amino acid sequence of SEQ ID NO: 6; a FR2 having the amino acid sequence of WVRQAPGQGLEWMG (SEQ ID NO: 7) or an amino acid sequence having one or more amino acid alterations with the amino acid sequence of SEQ ID NO: 7; a FR3 having the amino acid sequence of RFVFSLDTSVSTANLQISSLKAEDTAVYFCAR (SEQ ID NO: 8) or an amino acid 7107489sequence having one or more amino acid alterations with the amino acid sequence of SEQ ID NO: 8; and / or a FR4 having the amino acid sequence of WGQGTLVTVSS (SEQ ID NO: 9) or an amino acid sequence having one or more amino acid alterations with the amino acid sequence of SEQ ID NO: 5.[000172] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a heavy chain variable domain comprising a FR1 having one or more (two or more, three or more, four or more, five or more, six of more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, or fifteen or more) amino acid alterations with the amino acid sequence of QVQLVQSGSELKKPGESVKVSCKASGYTFT (SEQ ID NO: 6). In some embodiments, the FR1 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid alteration(s) with the amino acid sequence of QVQLVQSGSELKKPGESVKVSCKASGYTFT (SEQ ID NO: 6). In some embodiments, the FR1 comprises an alteration at one or more of the FR1 amino acid positions provided in Table 10 (e.g., at one or more positions corresponding to QI, V2, Q6, S9, E10, Lil, K12, K13, E16, S17, V18, K19, V20, K23, A24, G26, Y27, T28, F29, or T30 of SEQ ID NO: 1). In some embodiments, the FR1 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 of the alterations (FR1 Alterations) provided in Table 10. In some embodiments, the FR1 comprises a combination of alterations (FR1 Combination Alterations) provided in Table 10.[000173] In some embodiments, an anti-TCR[3V9 antibody provided herein comprises a heavy chain variable domain comprising a FR2 having one or more (two or more, three or more, four or more, or five or more) amino acid alterations with the amino acid sequence of WVRQAPGQGLEWMG (SEQ ID NO: 7). In some embodiments, the FR2 comprises 1, 2, 3, 4, or 5 amino acid alteration(s) with the amino acid sequence of WVRQAPGQGLEWMG (SEQ ID NO: 7). In some embodiments, the FR2 comprises an alteration at one or more of the FR2 amino acid positions provided in Table 10 (e.g., at one or more positions corresponding to W36, R38, Q43, G44, M48, or G49 of SEQ ID NO: 1). In some embodiments, the FR2 comprises 1, 2, 3, 4, or 5 of the alterations (FR2 Alterations) provided in Table 10. In some embodiments, the FR2 comprises a combination of alterations (FR2 Combination Alterations) provided in Table 10.[000174] In some embodiments, an anti-TCR[3V9 antibody provided herein comprises a heavy chain variable domain comprising a FR3 having one or more (two or more, three or more, four or more, five or more, six of more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, or fifteen or 7107489more) amino acid alterations with the amino acid sequence of RFVFSLDTSVSTANLQISSLKAEDTAVYFCAR (SEQ ID NO: 8). In some embodiments, the FR3 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid alteration(s) with the amino acid sequence of RFVFSLDTSVSTANLQISSLKAEDTAVYFCAR (SEQ ID NO: 8). In some embodiments, the FR3 comprises an alteration at one or more of the FR3 amino acid positions provided in Table 10 (e.g., at one or more positions corresponding to F68, V69, S71, T74, V76, T78, A79, N80, L81, Q82, 183, S84, S85, K87, A88, E89, A97, or R98 of SEQ ID NO: 1). In some embodiments, the FR3 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 of the alterations (FR3 Alterations) provided in Table 10. In some embodiments, the FR3 comprises a combination of alterations (FR3 Combination Alterations) provided in Table 10.[000175] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a heavy chain variable domain comprising a FR4 having one or more (two or more, three or more, or four or more) amino acid alterations with the amino acid sequence of WGQGTLVTVSS (SEQ ID NO: 9). In some embodiments, the FR4 comprises 1, 2, 3, or 4 amino acid alteration(s) with the amino acid sequence of WGQGTLVTVSS (SEQ ID NO: 9). In some embodiments, the FR4 comprises an alteration at one or more of the FR4 amino acid positions provided in Table 10 (e.g., at one or more positions corresponding to T116 or LI 17 of SEQ ID NO: 1). In some embodiments, the FR4 comprises 1, 2, 3, or 4 of the alterations (FR4 Alterations) provided in Table 10. In some embodiments, the FR4 comprises a combination of alterations (FR4 Combination Alterations) provided in Table 10.[000176] In some embodiments, an anti-TCR[3V9 antibody provided herein comprises a heavy chain variable framework 1 (HC FR1), a HC FR2, a HC FR3, and a HC FR4 comprising one or more (two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, fifteen or more, sixteen or more, seventeen or more, eighteen or more, nineteen or more, twenty or more, twenty-one or more, twenty-two or more, twenty-three or more, twenty-four or more, or twenty-five or more) alterations as compared to: a HC FR1 having the amino acid sequence of SEQ ID NO: 6; a HC FR2 having the amino acid sequence of SEQ ID NO: 7; a HC FR3 having the amino acid sequence of SEQ ID NO: 8; and a HC FR4 having the amino acid sequence of SEQ ID NO: 9. In some embodiments, the one or more (two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, fifteen or more, sixteen or more, seventeen or more, 7107489eighteen or more, nineteen or more, twenty or more, twenty-one or more, twenty-two or more, twenty-three or more, twenty-four or more, or twenty-five or more) alterations are provided in Table 10. In some embodiments, an anti-TCRpV9 antibody provided herein comprises a HC FR1, a HC FR2, a HC FR3, and a HC FR4 having a combination of alterations (“Alteration Combination FR1-4”) provided in Table 10.[000177] In some embodiments, a heavy chain variable domain comprises: a FR1 having the amino acid sequence of a FR1 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR1 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3; a FR2 having the amino acid sequence of a FR2 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR2 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3; a FR3 having the amino acid sequence of a FR3 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR3 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3; and / or a FR4 having the amino acid sequence of a FR4 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR4 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3. In some embodiments, FRs of a heavy chain variable domain are determined according to Kabat. In some embodiments, FRs of a heavy chain variable domain are determined according to Chothia. In some embodiments, FRs of a heavy chain variable domain are determined according to IMGT. In some embodiments, FRs of a heavy chain variable domain are determined according to AbM. In some embodiments, FRs of a heavy chain variable domain are determined according to Contact.Table 10. Alterations (“Alt.”) and Alteration Combinations of Exemplary Variable Heavy FRs. Positions correspond to the sequential positions (1-122) of SEQ ID NO: 1. For corresponding Kabat, Chothia, AbM, Contact, and IMGT numbering, see FIG. 1.710748971074897107489710748971074897107489[000178] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a HC FR1 provided in Table 11. In some embodiments, an anti-TCRpV9 antibody comprises a HC FR1 that has no more than 15 amino acid alterations (e.g., no more than 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alterations) as compared to a HC FR1 provided in Table 11. In some embodiments, an anti-TCRpV9 antibody comprises a HC FR1 that is at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a HC FR1 provided in Table 11.7107489[000179] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a HC FR2 provided in Table 11. In some embodiments, an anti-TCRpV9 antibody comprises a HC FR2 that has no more than 5 amino acid alterations (e.g., no more than 5, 4, 3, 2, or 1 amino acid alterations) as compared to a HC FR2 provided in Table 11. In some embodiments, an anti-TCRpV9 antibody comprises a HC FR2 that is at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a HC FR2 provided in Table 11.[000180] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a HC FR3 provided in Table 11. In some embodiments, an anti-TCRpV9 antibody comprises a HC FR3 that has no more than 15 amino acid alterations (e.g., no more than 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alterations) as compared to a HC FR3 provided in Table 11. In some embodiments, an anti-TCRpV9 antibody comprises a HC FR3 that is at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a HC FR3 provided in Table 11.[000181] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a HC FR4 provided in Table 11. In some embodiments, an anti-TCRpV9 antibody comprises a HC FR4 that has no more than 4 amino acid alterations (e.g., no more than 4, 3, 2, or 1 amino acid alterations) as compared to a HC FR4 provided in Table 11. In some embodiments, an anti-TCRpV9 antibody comprises a HC FR4 that is at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a HC FR4 provided in Table 11.[000182] In some embodiments, an anti-TCRpV9 antibody of the present disclosure comprises a HC FR1, a HC FR2, a HC FR3, and a HC FR4 combination provided in Table 11. In some embodiments, an anti-TCRpV9 antibody comprises a HC FR1, a HC FR2, a HC FR3, and a HC FR4 collectively having no more than 25 amino acid alterations (e.g., no more than 25, 24, 23, 22, 21, 20, 19, 28, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alterations) as compared to a HC FR1, a HC FR2, a HC FR3, and a HC FR4 combination provided in Table 11. In some embodiments, an anti-TCRpV9 comprises a HC FR1, a HC FR2, a HC FR3, and a HC FR4, that is collectively at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a HC FR1, a HC FR2, a HC FR3, and a HC FR4 combination provided in Table 11.7107489Table 11. Amino Acid Sequences of Exemplary Variable Heavy FRs and FR Combinations. FRs are provided according to Kabat numbering.7107489710748971074897107489[000183] In some embodiments, an anti-TCRpV9 antibody comprises a heavy chain having an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) to an amino acid sequence provided in Table 3. In some embodiments, an anti-TCRpV9 antibody comprises a heavy chain comprising any one of FR1, FR2, FR3, or FR4 provided in Table 11. In some embodiments, an anti-TCRPV9 antibody comprises a heavy chain comprising a combination of an FR1, an FR2, an FR3, and an FR4 provided in Table 11. In some embodiments, an anti-TCRpV9 antibody comprises a heavy chain comprising an FR combination (i.e. a combination of FR1, FR2, FR3, and FR4) provided in Table 11.[000184] In some embodiments, an anti-TCRpV9 antibody provided herein does not comprise a HC FR1-4 combination of the antibody BL37.2. See e.g., WO 2020 / 010250 A2, 7107489Table 10A. In some embodiments, an anti-TCRpV9 antibody provided herein does not comprise a HC FR1-4 combination of an antibody disclosed in WO 2019 / 132738 Al, WO 2020 / 139171 Al, WO 2020 / 139175 A2, WO 2023 / 146437 Al, or WO 2024 / 039268 Al.[000185] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid sequence of QIQLVQSGPELREPGESVKLSCKASGYTFTDYLVHWVKQAPGKGLKWMGWINTYT GTPTYADDFEGRFVFSLEASASTANLQISNLKNEDTATYFCARSWRRGLRGLGFDY WGQGVFVTVSS (SEQ ID NO: 1015).[000186] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid sequence of QIQLVQSGPELREPGESVKLSCKASGYTFTDYLVHWVKQAPGKGLKWMGWINTYT GTPTYADDFEGRFVFSLEASASTANLQISNLKNEDTATYFCARSWRRGLRGIGFDYW GQGVFVTVSS (SEQ ID NO: 1016).[000187] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid sequence of QIQLVQSGPELREPGESVKLSCKASGYTFTDYLVHWVKQAPGKGLKWMGWINTYT GTPTYADDFEGRFVFSLEASASTANLQISNLKNEDTATYFCARSWRRGIRGLGFDYW GQGVFVTVSS (SEQ ID NO: 1017).[000188] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid sequence of QIQLVQSGPELREPGESVKLSCKASGYTFTDYLVHWVKQAPGKGLKWMGWINTYT GTPTYADDFEGRFVFSLEASASTANLQISNLKNEDTATYFCARSWRRGIRGIGFDYW GQGVFVTVSS (SEQ ID NO: 1018).[000189] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid sequence of QIQLVQSGPELKEPGESVKISCKASGYTFTDYLVHWVKQAPGKGIKWMGWINTYTG TPTYADDFEGRFVFSIEASASTANLQISNIKNEDTATYFCARSWRRGLRGLGFDY(SEQ ID NO: 1019).[000190] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid sequence of QIQLVQSGPEIKEPGESVKISCKASGYTFTDYLVHWVKQAPGKGIKWMGWINTYTGT PTYADDFEGRFVFSIEASASTANLQISNIKNEDTATYFCARSWRRGLRGLGFDY (SEQ ID NO: 1020).[000191] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid 7107489sequence of QVQLVQSGPELKKPGESVKVSCKASGYTFTDYLVHWVRQAPGKGLEWMGWINTYT GTPTYADDFEGRFVFSLDTSASTANLQICSLKNEDTATYYCARSWRRGLRGIGFDYW GQGTEVTVSS (SEQ ID NO: 1021).[000192] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid sequence of QLQLVQSGPELREPGESVKISCKASGYTFTDYIVHWVKQAPGKGLKWMGWINTYTG TPTYADDFEGRFVFSEEASASTANEQISNEKNEDTATYFCARSWRRGIRGIGFDYWG QGVMVTVSS (SEQ ID NO: 1022).[000193] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid sequence of QLQLVQSGAEVKKPGASVKVSCKASGYTFTDYIVHWVRQAPGQGLEWMGWINTYT GTPTYADDFEGWVTMTLDASISTAYMELSRLRSDDTAVYYCARSWRRGIRGIGFDY WGQGTMVTVSS (SEQ ID NO: 1023).[000194] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid sequence of QLQLVQSGAEVKKPGASVKVSCKASGYTFTDYIVHWVRQAPGQGLEWMGWINTYT GTPTYADDFEGRVTMTLDASTSTAYMELSSLRSEDTAVYYCARSWRRGIRGIGFDY WGQGTMVTVSS (SEQ ID NO: 1024).[000195] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid sequence of QLQLVQSGAEVKKPGASVKVSCKASGYTFTDYIVHWVRQAPGQRLEWMGWINTYT GTPTYADDFEGRVTITLDASASTAYMELSSLRSEDMAVYYCARSWRRGIRGIGFDY WGQGTMVTVSS (SEQ ID NO: 1025).[000196] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid sequence of QLQLVQSGAEVKKPGASVKVSCKASGYTFTDYIVHWVRQATGQGLEWMGWINTYT GTPTYADDFEGRVTMTLNASISTAYMELSSLRSEDTAVYYCARSWRRGIRGIGFDYW GQGTMVTVSS (SEQ ID NO: 1026).B. Light Chain Variable Domains[000197] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a light chain variable domain having increased affinity to TCRPV9 relative to a light chain variable domain consisting of the amino acid sequence of SEQ ID NO: 2.7107489[000198] In some embodiments, the disclosure provides a TCRPV9 targeting molecule comprising an antibody that specifically binds to TCRPV9, wherein the antibody comprises a light chain variable domain comprising: a CDR1 having the amino acid sequence of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with a CDR1 of a light chain variable domain comprising an amino acid sequence provided in Table 6; a CDR2 having the amino acid sequence of a CDR2 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 3, 2, or 1 amino acid alteration (s) with a CDR2 of a light chain variable domain comprising an amino acid sequence provided in Table 6; and / or a CDR3 having the amino acid sequence of a CDR3 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with a CDR3 of a light chain variable domain comprising an amino acid sequence provided in Table 6. In some embodiments, CDRs of a light chain variable domain are determined according to Kabat. In some embodiments, CDRs of a light chain variable domain are determined according to Chothia. In some embodiments, CDRs of a light chain variable domain are determined according to IMGT. In some embodiments, CDRs of a light chain variable domain are determined according to AbM. In some embodiments, CDRs of a light chain variable domain are determined according to Contact.[000199] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a light chain variable domain, wherein the light chain variable domain comprises: a CDR1 having the amino acid sequence of KASKSINKYL (SEQ ID NO: 10) or an amino acid sequence having one or more amino acid alterations with the amino acid sequence of SEQ ID NO: 10; a CDR2 having the amino acid sequence of DGSTLQS (SEQ ID NO: 11) or an amino acid sequence having one or more amino acid alterations with the amino acid sequence of SEQ ID NO: 11; and a CDR3 having the amino acid sequence of QQHNEYPPT (SEQ ID NO: 12) or an amino acid sequence having one or more amino acid alterations with the amino acid sequence of SEQ ID NO: 12.[000200] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a light chain variable domain comprising a CDR1 having one or more (2 or more or 3 or more) amino acid alterations with the amino acid sequence of KASKSINKYL (SEQ ID NO: 10). In some embodiments, the CDR1 comprises 1, 2, or 3 amino acid alteration(s) with the amino acid sequence of KASKSINKYL (SEQ ID NO: 10). In some embodiments, the CDR1 comprises an alteration at one or more of the CDR1 amino acid positions provided in Table 710748912 (e.g., at one or more positions corresponding to K24, A25, S26, K27, S28, 129, N30, K31, Y32, or L33 of SEQ ID NO: 2). In some embodiments, the CDR1 comprises 1, 2, or 3 of the alterations (CDR1 Alterations) provided in Table 12. In some embodiments, the CDR1 comprises a combination of alterations (CDR1 Combination Alterations) provided in Table 12.[000201] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a light chain variable domain comprising a CDR2 having one or more (2 or more, 3 or more, 4 or more, or 5 or more) amino acid alterations with the amino acid sequence of DGSTLQS (SEQ ID NO: 11). In some embodiments, the CDR2 comprises 1, 2, 3, 4, or 5 amino acid alteration(s) with the amino acid sequence of DGSTLQS (SEQ ID NO: 11). In some embodiments, the CDR2 comprises an alteration at one or more of the CDR2 amino acid positions provided in Table 12 e.g., at one or more positions corresponding to D50, G51, S52, T53, L54, Q55, or S56 of SEQ ID NO: 2). In some embodiments, the CDR2 comprises 1, 2, 3, 4, or 5 of the alterations (CDR2 Alterations) provided in Table 12. In some embodiments, the CDR2 comprises a combination of alterations (CDR2 Combination Alterations) provided in Table 12.[000202] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a light chain variable domain comprising a CDR3 having one or more (2 or more, 3 or more, 4 or more, or 5 or more) amino acid alterations with the amino acid sequence of QQHNEYPPT (SEQ ID NO: 12). In some embodiments, the CDR3 comprises 1, 2, 3, 4, or 5 amino acid alteration(s) with the amino acid sequence of QQHNEYPPT (SEQ ID NO: 12). In some embodiments, the CDR3 comprises an alteration at one or more of the CDR3 amino acid positions provided in Table 12 (e.g., at one or more positions corresponding to Q89, Q90, H91, N92, E93, Y94, P95, P96, or T97 of SEQ ID NO: 2). In some embodiments, the CDR3 comprises 1, 2, 3, 4, or 5 of the alterations (CDR3 Alterations) provided in Table 12. In some embodiments, the CDR3 comprises a combination of alterations (CDR3 Combination Alterations) provided in Table 12.[000203] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a light chain complementarity determining region 1 (LC CDR1), a LC CDR2, and a LC CDR3 comprising one or more (two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, or ten or more) alterations as compared to: a LC CDR1 having the amino acid sequence of SEQ ID NO: 10; a LC CDR2 having the amino acid sequence of SEQ ID NO: 11; and a LC CDR3 having the amino acid sequence of SEQ ID NO: 12. In some embodiments, the one or more (two or more, three or more, four or more, 7107489five or more, six or more, seven or more, eight or more, nine or more, or ten or more) alterations are provided in Table 12. In some embodiments, an anti-TCRpV9 antibody provided herein comprises a LC CDR1, a LC CDR2, and LC CDR3 having a combination of alterations (CDR 1-3 Alteration Combination) provided in Table 12. Variable light domain CDRs referred to herein can be determined according to any CDR numbering convention (e.g., Kabat, Chothia, AbM, Contact, and IMGT, as shown in FIG. 2).Table 12. Alterations and Alteration Combinations of Exemplary Variable Light CDRs. Positions correspond to the sequential positions (1-107) of SEQ ID NO: 2. For corresponding Kabat, Chothia, AbM, Contact, and IMGT numbering, see FIG. 2.[000204] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a EC CDR1 provided in Table 13. In some embodiments, an anti-TCRpV9 antibody comprises a EC CDR1 that has no more than 5 amino acid alterations (e.g., no more than 5, 4, 3, 2, or 1 amino acid alterations) as compared to a LC CDR1 provided in Table 13. In some embodiments, an anti-TCRpV9 antibody comprises a LC CDR1 that is at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a HC CDR1 provided in Table 13.[000205] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a LC7107489CDR2 provided in Table 13. In some embodiments, an anti-TCRpV9 antibody comprises a LC CDR2 that has no more than 5 amino acid alterations (e.g., no more than 5, 4, 3, 2, or 1 amino acid alterations) as compared to a LC CDR2 provided in Table 13. In some embodiments, an anti-TCRpV9 antibody comprises a LC CDR2 that is at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a LC CDR2 provided in Table 13.[000206] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a LC CDR3 provided in Table 13. In some embodiments, an anti-TCRpV9 antibody comprises a LC CDR3 that has no more than 5 amino acid alterations (e.g., no more than 5, 4, 3, 2, or 1 amino acid alterations) as compared to a LC CDR3 provided in Table 13. In some embodiments, an anti-TCRpV9 antibody comprises a LC CDR3 that is at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a LC CDR3 provided in Table 13.[000207] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a LC CDR1, a LC CDR2, and a LC CDR3 combination provided in Table 13. In some embodiments, an anti-TCRpV9 antibody comprises a LC CDR1, a LC CDR2, and a LC CDR3 combination that collectively has no more than 5 amino acid alterations (e.g., no more than 5, 4, 3, 2, or 1 amino acid alterations) as compared to a LC CDR1, a LC CDR2, and a LC CDR3 combination provided in Table 13. In some embodiments, an anti-TCRpV9 antibody comprises a LC CDR1, a LC CDR2, and a LC CDR3 combination that is collectively at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a LC CDR1, a LC CDR2, and a LC CDR3 combination provided in Table 13.Table 13. Amino Acid Sequences of Exemplary Variable Light CDRs and CDR Combinations. CDRs are provided according to Kabat numbering.71074897107489[000208] In some embodiments, an anti-TCRpV9 antibody provided herein does not comprise a LC CDR1-3 combination of the antibody BL37.2. See e.g., WO 2020 / 010250 A2, Table 10A. In some embodiments, an anti-TCRpV9 antibody provided herein does not comprise a LC CDR1-3 combination of an antibody disclosed in WO 2019 / 132738 Al, WO 2020 / 139171 Al, WO 2020 / 139175 A2, WO 2023 / 146437 Al, or WO 2024 / 039268 Al.[000209] In some embodiments, an anti-TCRpV9 antibody does not comprise the combination of: a LC CDR1 consisting of the amino acid sequence of KASKSINKYL (SEQ ID NO: 10); a LC CDR2 consisting of the amino acid sequence of DGSTLQS (SEQ ID NO: 11); and a LC CDR3 consisting of the amino acid sequence of QQHNEYPPT (SEQ ID NO: 12), wherein the CDRs are determined according to Kabat numbering.[000210] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a light chain variable domain comprising: a FR1 having the amino acid sequence of DIQMTQSPYSLSASVGDRVTITC (SEQ ID NO: 13) or an amino acid sequence having one or more amino acid alterations with the amino acid sequence of SEQ ID NO: 13; a FR2 having the amino acid sequence of AWFQQKPGKPNKLLIY (SEQ ID NO: 14) or an amino acid sequence having one or more amino acid alterations with the amino acid sequence of SEQ ID NO: 14; a FR3 having the amino acid sequence of GVPSRFSGSGSGTDFTLTISSLEPEDFATYYC (SEQ ID NO: 15) or an amino acid sequence having one or more amino acid alterations with the amino acid sequence of SEQ ID NO: 15; and / or a FR4 having the amino acid sequence of FGQGTKLEIK (SEQ ID NO: 16) or an amino acid sequence having one or more amino acid alterations with the amino acid7107489sequence of SEQ ID NO: 16.[000211] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a light chain variable domain comprising a FR1 having one or more (two or more, three or more, four or more, five or more, six of more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, or fifteen or more) amino acid alterations with the amino acid sequence of DIQMTQSPYSLSASVGDRVTITC (SEQ ID NO: 13). In some embodiments, the FR1 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid alteration(s) with the amino acid sequence of DIQMTQSPYSLSASVGDRVTITC (SEQ ID NO: 13). In some embodiments, the FR1 comprises an alteration at one or more of the FR1 amino acid positions provided in Table 14 (e.g., at one or more positions corresponding to DI, 12, Q3, S7, Y9, S10, Lil, S12, A13, S14, V15, D17, R18, V19, T20, 121, or T22 of SEQ ID NO: 2). In some embodiments, the FR1 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 of the alterations (FR1 Alterations) provided in Table 14. In some embodiments, the FR1 comprises a combination of alterations (FR1 Combination Alterations) provided in Table 14.[000212] In some embodiments, an anti-TCR[3V9 antibody provided herein comprises a light chain variable domain comprising a FR2 having one or more (two or more, three or more, four or more, five or more, or six or more) amino acid alterations with the amino acid sequence of AWFQQKPGKPNKLLIY (SEQ ID NO: 14). In some embodiments, the FR2 comprises 1, 2, 3, 4, 5, or 6 amino acid alteration(s) with the amino acid sequence of AWFQQKPGKPNKLLIY (SEQ ID NO: 14). In some embodiments, the FR2 comprises an alteration at one or more of the FR2 amino acid positions provided in Table 14 e.g., at one or more positions corresponding to A34, F36, Q37, K39, G41, K42, P43, N44, K45, or L47 of SEQ ID NO: 2). In some embodiments, the FR2 comprises 1, 2, 3, 4, or 5 of the alterations (FR2 Alterations) provided in Table 14. In some embodiments, the FR2 comprises a combination of alterations (FR2 Combination Alterations) provided in Table 14.[000213] In some embodiments, an anti-TCR[3V9 antibody provided herein comprises a light chain variable domain comprising a FR3 having one or more (two or more, three or more, four or more, five or more, six of more, seven or more, eight or more, nine or more, or ten or more) amino acid alterations with the amino acid sequence of GVPSRFSGSGSGTDFTLTISSLEPEDFATYYC (SEQ ID NO: 15). In some embodiments, the FR3 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid alteration(s) with the amino acid sequence of GVPSRFSGSGSGTDFTLTISSLEPEDFATYYC (SEQ ID NO: 15). In some embodiments, the FR3 comprises an alteration at one or more of the FR3 amino acid7107489positions provided in Table 14 (e.g., at one or more positions corresponding to G57, V58, S60, S67, D70, L73, T74, S76, S77, L78, E79, P80, F83, A84, T85, or Y87 of SEQ ID NO: 2). In some embodiments, the FR3 comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 of the alterations (FR3 Alterations) provided in Table 14. In some embodiments, the FR3 comprises a combination of alterations (FR3 Combination Alterations) provided in Table 14.[000214] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a light chain variable domain comprising a FR4 having one or more (two or more, three or more, or four or more) amino acid alterations with the amino acid sequence of FGQGTKLEIK (SEQ ID NO: 16). In some embodiments, the FR4 comprises 1, 2, 3, or 4 amino acid alteration(s) with the amino acid sequence of FGQGTKLEIK (SEQ ID NO: 16).[000215] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a light chain variable framework 1 (LC FR1), a LC FR2, a LC FR3, and a LC FR4 comprising one or more (two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, fifteen or more, sixteen or more, seventeen or more, eighteen or more, nineteen or more, twenty or more, twenty-one or more, twenty-two or more, twenty-three or more, twenty-four or more, or twenty-five or more) alterations as compared to: a LC FR1 having the amino acid sequence of SEQ ID NO: 13; a LC FR2 having the amino acid sequence of SEQ ID NO: 14; a LC FR3 having the amino acid sequence of SEQ ID NO: 15; and a LC FR4 having the amino acid sequence of SEQ ID NO: 16. In some embodiments, the one or more (two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, fifteen or more, sixteen or more, seventeen or more, eighteen or more, nineteen or more, twenty or more, twenty-one or more, twenty-two or more, twenty-three or more, twenty-four or more, or twenty-five or more) alterations are provided in Table 14. In some embodiments, an anti-TCRpV9 antibody provided herein comprises a LC FR1, a LC FR2, a LC FR3, and a LC FR4 having a combination of alterations (FR 1-4 Alteration Combination) provided in Table 14.[000216] In some embodiments, a light chain variable domain comprises: a FR1 having the amino acid sequence of a FR1 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR1 of a light chain variable domain comprising an amino acid sequence provided in Table 6; a FR2 having the amino acid sequence of a FR2 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence 7107489having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR2 of a light chain variable domain comprising an amino acid sequence provided in Table 6; a FR3 having the amino acid sequence of a FR3 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR3 of a light chain variable domain comprising an amino acid sequence provided in Table 6; and / or a FR4 having the amino acid sequence of a FR4 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR4 of a light chain variable domain comprising an amino acid sequence provided in Table 6. In some embodiments, FRs of a light chain variable domain are determined according to Kabat. In some embodiments, FRs of a light chain variable domain are determined according to Chothia. In some embodiments, FRs of a light chain variable domain are determined according to IMGT. In some embodiments, FRs of a light chain variable domain are determined according to AbM. In some embodiments, FRs of a light chain variable domain are determined according to Contact.Table 14. Alterations (“Alt.”) and Combinations of Exemplary Variable Light FRs.Positions correspond to the sequential positions (1-107) of SEQ ID NO: 2. For corresponding Kabat, Chothia, AbM, Contact, and IMGT numbering, see FIG. 2.7107489[000217] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a LC FR1 provided in Table 15. In some embodiments, an anti-TCRpV9 antibody comprises a LC FR1 that has no more than 10 amino acid alterations (e.g., no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alterations) as compared to a LC FR1 provided in Table 15. In some embodiments, an anti-TCRpV9 antibody comprises a LC FR1 that is at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a LC FR1 provided in Table 15.[000218] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a LC7107489FR2 provided in Table 15. In some embodiments, an anti-TCRpV9 antibody comprises a LC FR2 that has no more than 5 amino acid alterations (e.g., no more than 5, 4, 3, 2, or 1 amino acid alterations) as compared to a LC FR2 provided in Table 15. In some embodiments, an anti-TCRpV9 antibody comprises a LC FR2 that is at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a LC FR2 provided in Table 15.[000219] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a LC FR3 provided in Table 15. In some embodiments, an anti-TCRpV9 antibody comprises a LC FR3 that has no more than 10 amino acid alterations (e.g., no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alterations) as compared to a LC FR3 provided in Table 15. In some embodiments, an anti-TCRpV9 antibody comprises a LC FR3 that is at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a LC FR3 provided in Table 15.[000220] In some embodiments, an anti-TCRpV9 antibody provided herein comprises a LC FR4 provided in Table 15. In some embodiments, an anti-TCRpV9 antibody comprises a LC FR4 that has no more than 4 amino acid alterations (e.g., no more than 4, 3, 2, or 1 amino acid alterations) as compared to a LC FR4 provided in Table 15. In some embodiments, an anti-TCRpV9 antibody comprises a LC FR4 that is at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a LC FR4 provided in Table 15.[000221] In some embodiments, an anti-TCRpV9 antibody of the present disclosure comprises a LC FR1, a LC FR2, a LC FR3, and a LC FR4 combination selected from Table 15. In some embodiments, an anti-TCRpV9 antibody comprises a LC FR1, a LC FR2, a LC FR3, and a LC FR4 collectively having no more than 25 amino acid alterations (e.g., no more than 25, 24, 23, 22, 21, 20, 19, 28, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alterations) as compared to a LC FR1, a LC FR2, a LC FR3, and a LC FR4 combination provided in Table 15. In some embodiments, an anti-TCRpV9 comprises a LC FR1, a LC FR2, a LC FR3, and a LC FR4, that is collectively at least 80% (e.g., at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to a LC FR1, a LC FR2, a LC FR3, and a LC FR4 combination provided in Table 15.7107489Table 15. Amino Acid Sequences of Exemplary Variable Light FRs and FR Combinations.FRs are provided according to Kabat numbering.7107489[000222] In some embodiments, an anti-TCRpV9 antibody comprises a light chain having an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) to an amino acid sequence provided in Table 6. In some embodiments, an anti-TCRpV9 antibody comprises a light chain comprising any one of FR1, FR2, FR3, or FR4 provided in Table 15. In some embodiments, an anti-TCRPV9 antibody comprises a light chain comprising a combination of an FR1, an FR2, an FR3, and an FR4 provided in Table 15. In some embodiments, an anti-TCRpV9 antibody comprises a light chain comprising an FR combination (i.e. a combination of FR1, FR2, FR3, and FR4) provided in Table 15.[000223] In some embodiments, an anti-TCRpV9 antibody provided herein does not comprise a LC FR1-4 combination of the antibody BL37.2. See e.g., WO 2020 / 010250 A2, Table 10A. In some embodiments, an anti-TCRpV9 antibody provided herein does not comprise a LC FR1-4 combination of an antibody disclosed in WO 2019 / 132738 Al, WO 2020 / 139171 Al, WO 2020 / 139175 A2, WO 2023 / 146437 Al, or WO 2024 / 039268 Al.[000224] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid sequence of DVQMTQSPYNLAASPGESVSINCKASKSINKYLAWYQQKPGKPNKLLIYDGSTLQSG IPSRFSGSGSGTDFTLTIRGLEPEDFGLYYCQQHNEYPPTFGAGTKLELK (SEQ ID NO: 1029).[000225] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid sequence of EVVMTQSPGTLSLSPGERATLSCKASKSINKYLAWYQQKPGQAPRLLIYDGSTLQSGI PDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQHNEYPPTFGQGTKLEIK (SEQ ID NO: 1030).[000226] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid sequence of EVVMTQSPATLSLSPGERATLSCKASKSINKYLAWYQQKPGQAPRLLIYDGSTLQSGI PARFSGSGSGTDFTLTISSLEPEDFAVYYCQQHNEYPPTFGQGTKLEIK (SEQ ID NO: 1031).7107489[000227] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid sequence of DVQMTQSPSSLSASVGDRVTITCKASKSINKYLAWYQQKPGKAPKLLIYDGSTLQSG VPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHNEYPPTFGQGTKLEIK (SEQ ID NO: 1032).[000228] In some embodiments, an anti-TCRpV9 antibody does not comprise the amino acid sequence of AVRMTQSPSSFSASTGDRVTITCKASKSINKYLAWYQQKPGKAPKLLIYDGSTLQSG VPSRFSGSGSGTDFTLTISCLQSEDFATYYCQQHNEYPPTFGQGTKLEIK (SEQ ID NO: 1033).C. Heavy, Light Variable Domain Pairs[000229] In some embodiments, anti-TCRpV9 antibodies of the present disclosure comprise the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 as provided for any one of the VH / VL pairs provided in Table 16. In some embodiments, antibody heavy and light chain CDR3 domains may play a particularly important role in the binding specificity / affinity of an antibody for an antigen. Accordingly, the anti-TCRpV9 antibodies of the disclosure may include at least the heavy chain CDR3s provided in Table 9 and / or light chain CDR3s provided in Table 13. In some embodiments, anti-TCRpV9 antibodies of the present disclosure comprise a HV, VL pair provided in Table 16.Table 16. Amino Acid Sequences of Exemplary VH / VL Pairs7107489710748971074897107489710748971074897107489[000230] Also within the scope of the present disclosure are functional variants of any of the exemplary anti-TCRpV9 antibodies as disclosed herein. A functional variant may contain one or more amino acid residue alterations in the VH and / or VL, or in one or more of the HC CDRs and / or one or more of the LC CDRs as relative to the reference antibody, while retaining substantially similar binding and biological activities (e.g., substantially similar binding affinity, binding specificity, inhibitory activity, anti-inflammatory activity, or a combination thereof) as the reference antibody.[000231] In some embodiments, any of the anti-TCRpV9 antibodies of the disclosure have one or more CDRs (e.g., HC CDR or LC CDR) sequences substantially similar to any of the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 sequences from one of the VH / VL pairs selected from Table 16. In some embodiments, the position of one or more CDRs along the VH (e.g., HC CDR1, HC CDR2, or HC CDR3) and / or VL (e.g., LC CDR1, LC CDR2, or LC CDR3) region of an antibody described herein can vary by one, two, three, four, five, or six amino acid positions so long as immuno specific binding to TCRPV9 (e.g., human TCRPV9) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived). For example, in some embodiments, the position defining a CDR of any antibody described herein can vary by shifting the N-terminal and / or C-terminal boundary of the CDR by one, two, three, four, five, or six amino acids, relative to the CDR position of any one of the antibodies described herein, so long as immuno specific binding to TCRPV9 (e.g., human TCRPV9) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived). In another embodiment, the length of one or more CDRs along the VH (e.g., HC CDR1, HC CDR2, or HC CDR3) and / or VL (e.g., LC CDR1, LC CDR2, or LC CDR3) region of an antibody described herein can vary (e.g., be shorter or longer) by one, two, three, four, five, or more7107489amino acids, so long as immuno specific binding to TCRPV9 (e.g., human TCRPV9) is maintained e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived).[000232] Accordingly, in some embodiments, a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein may be one, two, three, four, five or more amino acids shorter than one or more of the CDRs described herein (e.g., CDRs from any of the VH / VL pairs selected from Table 16) so long as immuno specific binding to TCRPV9 (e.g., human TCRPV9) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein may be one, two, three, four, five or more amino acids longer than one or more of the CDRs described herein (e.g., CDRs from any of the VH / VL pairs selected from Table 16) so long as immuno specific binding to TCRPV9 (e.g., human TCRPV9) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, the amino portion of a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be extended by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., CDRs from any of the VH / VL pairs selected from Table 16) so long as immuno specific binding to TCRPV9 (e.g., human TCRPV9) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, the carboxy portion of a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be extended by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., CDRs from any of the VH / VL pairs selected from Table 16) so long as immuno specific binding to TCRPV9 (e.g., human TCRPV9) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, the amino portion of a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be shortened by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., CDRs from any of the VH / VL pairs selected from Table 16) 7107489so long as immuno specific binding to TCRPV9 (e.g., human TCRPV9) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, the carboxy portion of a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be shortened by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein e.g., CDRs from any of the VH / VL pairs selected from Table 16) so long as immuno specific binding to TCRPV9 (e.g., human TCRPV9) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). Any method can be used to ascertain whether immuno specific binding to TCRPV9 (e.g., human TCRPV9) is maintained, for example, using binding assays and conditions described in the art.[000233] In some examples, any of the anti-TCRpV9 antibodies of the disclosure have one or more CDR (e.g., HC CDR or LC CDR) sequences substantially similar to any one of the VH / VL pairs selected from Table 16. For example, the antibodies may include one or more CDR sequence(s) from any of the VH / VL pairs selected from Table 16 containing up to 5, 4, 3, 2, or 1 amino acid residue alterations as compared to the corresponding CDR region in any one of the CDRs provided herein (e.g., CDRs from any of the VH / VL selected from Table 16) so long as immuno specific binding to TCRPV9 (e.g., human TCRPV9) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, any of the amino acid alterations in any of the CDRs provided herein may be conservative alterations. Conservative alterations can be introduced into the CDRs at positions where the residues are not likely to be involved in interacting with a TCRPV9 protein (e.g., a human TCRPV9 protein), for example, as determined based on a crystal structure. Some aspects of the disclosure provide anti-TCRpV9 antibodies that comprise one or more of the heavy chain variable (VH) and / or light chain variable (VL) domains provided herein. In some embodiments, any of the VH domains provided herein include one or more of the HC CDR sequences (e.g., HC CDR1, HC CDR2, and HC CDR3) provided herein, for example, any of the CDR-H sequences selected from Tables 8 or 9. In some embodiments, any of the VL domains provided herein include one or more of the CDR-L sequences (e.g., LC CDR1, LC CDR2, and LC CDR3) provided herein, for example, any of the LC CDR sequences selected from Tables 12 or 13.7107489[000234] In some embodiments, the anti-TCRpV9 antibodies of the disclosure include any antibody that includes a heavy chain variable domain and / or a light chain variable domain of any one of the VH / VL pairs selected from Table 16, and variants thereof. In some embodiments, anti-TCRpV9 antibodies of the disclosure include any antibody that includes the VH / VL pairs selected from Table 16.[000235] Aspects of the disclosure provide anti-TCRpV9 antibodies having a heavy chain variable (VH) and / or a light chain variable (VL) domain amino acid sequence homologous to any of those described herein. In some embodiments, the anti-TCRpV9 antibody comprises a heavy chain variable sequence or a light chain variable sequence that is at least 75% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the heavy chain variable sequence and / or any light chain variable sequence of any one of the VH and / or VL sequences selected from Table 16. In some embodiments, the homologous heavy chain variable and / or a light chain variable amino acid sequences do not vary within any of the CDR sequences provided herein. For example, in some embodiments, the degree of sequence alteration (e.g., 75%, 80%, 85%, 90%, 95%, 98%, or 99%) may occur within a heavy chain variable and / or a light chain variable sequence excluding any of the CDR sequences provided herein. In some embodiments, any of the anti-TCRpV9 antibodies provided herein comprise a heavy chain variable sequence and a light chain variable sequence that comprises a framework sequence that is at least 75%, 80%, 85%, 90%, 95%, 98%, or 99% identical to the framework sequence of any of the framework sequences selected from Tables 11 and / or 15.[000236] In some embodiments, the anti-TCRpV9 antibody of the present disclosure is a humanized antibody (e.g., a humanized variant containing one or more CDRs of Tables 9 and / or 13). In some embodiments, the anti-TCRpV9 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, a HC CDR3, a LC CDR1, a LC CDR2, and a LC CDR3 that are the same as the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 shown in Tables 9 and / or 13, and comprises a humanized heavy chain variable region and / or a humanized light chain variable region.[000237] In some embodiments, the anti-TCRpV9 antibody of the present disclosure is a humanized antibody comprising a VH containing no more than 20 amino acid alterations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alteration) as compared with any one of the VH domains listed in Table 16.Alternatively or in addition, the anti-TCRpV9 antibody of the present disclosure is a humanized antibody comprising a VL containing no more than 20 amino acid alterations7107489(e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alteration) as compared with any one of the VL domains listed in Table 16.[000238] In some embodiments, the anti-TCRpV9 antibody of the present disclosure is a chimeric antibody, which can include a heavy constant region and a light constant region from a human antibody. Chimeric antibodies refer to antibodies having a variable region or part of variable region from a first species and a constant region from a second species.Typically, in these chimeric antibodies, the variable region of both light and heavy chains mimics the variable regions of antibodies derived from one species of mammals (e.g., a nonhuman mammal such as mouse, rabbit, and rat), while the constant portions are homologous to the sequences in antibodies derived from another mammal such as human. In some embodiments, amino acid modifications can be made in the variable region and / or the constant region.[000239] In some embodiments, the anti-TCRpV9 antibody described herein is a chimeric antibody, which can include a heavy constant region and a light constant region from a human antibody. Chimeric antibodies refer to antibodies having a variable region or part of variable region from a first species and a constant region from a second species. Typically, in these chimeric antibodies, the variable region of both light and heavy chains mimics the variable regions of antibodies derived from one species of mammals (e.g., a non-human mammal such as mouse, rabbit, and rat), while the constant portions are homologous to the sequences in antibodies derived from another mammal such as human. In some embodiments, amino acid modifications can be made in the variable region and / or the constant region.[000240] In some embodiments, the anti-TCRpV9 antibody of the present disclosure comprises a VL domain and / or VH domain of any one of the VH / VL pairs selected from Table 16, and comprises a constant region comprising the amino acid sequences of the constant regions of an IgG, IgE, IgM, IgD, IgA or IgY immunoglobulin molecule, any class (e.g., IgGl, IgG2, IgG3, IgG4, IgAl and IgA2), or any subclass (e.g., IgG2a and IgG2b) of immunoglobulin molecule. Non-limiting examples of human constant regions are described in the art, e.g., see Kabat E A et al., (1991) supra.[000241] In some embodiments, the light chain of any of the anti-TCRpV9 antibodies described herein may further comprise a light chain constant region (CL), which can be any CL known in the art. In some examples, the CL is a kappa light chain. In other examples, the CL is a lambda light chain. In some embodiments, the CL is a kappa light chain.7107489[000242] Other antibody heavy and light chain constant regions are well known in the art, e.g., those provided in the IMGT database (imgt.org) or at vbase2.org / vbstat.php., both of which are incorporated by reference herein.[000243] In some embodiments, a TCRPV9 targeting molecule comprising a VH domain and VL domain provided herein, such as an Exemplary Polypeptide Pair from Table 7 herein, is improved, for example has improved function and / or properties compared to a comparator antibody (e.g., an antibody comprising a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 1 and a light chain variable domain having the amino acid sequence of SEQ ID NO: 2), for example wherein the comparator antibody has the same sequences outside of the heavy chain variable domain and the light chain variable domain as the TCRPV9 targeting molecule comprising a VH domain and VL domain provided herein (i.e. in the CHI, hinge, CH2 and CH3 of the heavy chain, and the CL of the light chain). These improvements include binding properties (strength and selectivity), potency, activity, safety, stability, and / or developability. Accordingly, in some embodiments, relative to a TCRPV9 targeting molecule comprising a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 1 and a light chain variable domain having the amino acid sequence of SEQ ID NO: 2, a TCRPV9 targeting molecule provided herein has a greater affinity for TCRPV9; increased selectivity; and / or increased human cell killing.[000244] In some embodiments, relative to a TCRPV9 targeting molecule comprising a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 1 and a light chain variable domain having the amino acid sequence of SEQ ID NO: 2, a TCRPV9 targeting molecule provided herein has a greater affinity for TCRPV9 as determined by surface plasma resonance at 25°C and a pH of 7.4 (optionally in conditions comprising lOmM HEPES buffer and 150 mM NaCl). In some embodiments, relative to a TCRPV9 targeting molecule comprising a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 1 and a light chain variable domain having the amino acid sequence of SEQ ID NO: 2, a TCRPV9 targeting molecule provided herein has a greater affinity for human TCRPV9 as determined by surface plasma resonance at 25°C and a pH of 7.4 (optionally in conditions comprising lOmM HEPES buffer and 150 mM NaCl). In some embodiments, a TCRPV9 targeting molecule provided herein has 1.1 times (l.lx), 1.2x, 1.3x, 1.4, 1.5x, 1.6x, 1.7x, 1.8x, 1.9x, 2x, 2.5x, 3x, 3.5x, 4x, 4.5x, 5x, or greater affinity for human TCRPV9 relative to a TCRPV9 targeting molecule comprising a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 1 and a light chain variable domain having the amino acid sequence of SEQ ID NO: 2 as determined by surface plasma resonance at 25°C and a pH of 71074897.4 (optionally in conditions comprising lOmM HEPES buffer and 150 mM NaCl). In some embodiments, greater affinity corresponds to a lower KD value (defined elsewhere herein). In some embodiments, a TCRPV9 targeting molecule provided herein has a KD value of less than or equal to (<) 1.7 x 10’9, 1.5 x 10’9, 1.3 x 10’9, 1.1 x 10’9, 1.0 x 10’9, 9 x IO10, 8.5 x 10’10, 8 x IO’10, 7.5 x IO’10, 7 x IO’10, 6 x IO’10, 5 x IO’10, 4 x IO’10, 3 x IO’10, 2 x IO’10, 1 x IO’10, 9 x IO’11, 8 x IO’11, 7 x IO’11, 6 x IO’11, 5 x IO’11, 4 x IO’11, 3 x IO’11, 2 x IO’11, 1 x IO’11, or lower. In some embodiments, a TCRPV9 targeting molecule provided herein has a KD value of less than or equal to 1.7 x 10’9.[000245] In some embodiments, relative to a TCRPV9 targeting molecule comprising a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 1 and a light chain variable domain having the amino acid sequence of SEQ ID NO: 2, a TCRPV9 targeting molecule provided herein has a greater affinity for TCRPV9 as determined by a cell binding assay using primary human TRBV9+ T cells, isolated from peripheral blood mononuclear cells (PBMCs), and serially diluted antibodies incubated with the cells for 1 hour at 4°C. In some embodiments, relative to a TCRPV9 targeting molecule comprising a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 1 and a light chain variable domain having the amino acid sequence of SEQ ID NO: 2, a TCRPV9 targeting molecule provided herein has a greater affinity for human TCRPV9 as determined by a cell binding assay using primary human TRBV9+ T cells, isolated from peripheral blood mononuclear cells (PBMCs), and serially diluted antibodies incubated with the cells for 1 hour at 4°C. In some embodiments, a TCRPV9 targeting molecule provided herein has 1.1 times (l.lx), 1.2x, 1.3x, 1.4, 1.5x, 1.6x, 1.7x, 1.8x, 1.9x, 2x, 2.5x, 3x, 3.5x, 4x, 4.5x, 5x, or greater affinity for human TCRPV9 relative to a TCRPV9 targeting molecule comprising a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 1 and a light chain variable domain having the amino acid sequence of SEQ ID NO: 2 as determined by a cell binding assay using primary human TRBV9+ T cells, isolated from peripheral blood mononuclear cells (PBMCs), and serially diluted antibodies incubated with the cells for 1 hour at 4°C. In some embodiments, greater affinity corresponds to a lower EC50 value. In some embodiments, a TCRPV9 targeting molecule provided herein has an cell binding EC50 of less than or equal to 3.25, 3, 2.75, 2.5, 2.25, 2, 1.75, 1.5, 1.25, 1, 0.75, 0.5, 0.25, or lower. In some embodiments, a TCRPV9 targeting molecule provided herein has an cell binding EC50 of less than or equal to 3.2.[000246] In some embodiments, relative to a TCRPV9 targeting molecule comprising a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 1 and a light 7107489chain variable domain having the amino acid sequence of SEQ ID NO: 2, a TCRPV9 targeting molecule provided herein has increased cell killing (e.g., of human cells or nonhuman primate, e.g., cynomolgus, cells expressing TCRPV9). In some embodiments, a TCRPV9 targeting molecule provided herein has l.lx, 1.2x, 1.3x, 1.4, 1.5x, 1.6x, 1.7x, 1.8x, 1.9x, 2x, 2.5x, 3x, 3.5x, 4x, 4.5x, 5x, or greater cell killing (e.g., of human cells or nonhuman primate, e.g., cynomolgus, cells expressing TCRPV9) relative to a TCRPV9 targeting molecule comprising a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 1 and a light chain variable domain having the amino acid sequence of SEQ ID NO: 2. In some embodiments, increased cell killing corresponds to lower EC50 in a human cell killing assay. In some embodiments, a TCRPV9 targeting molecule provided herein has a human cell killing EC50 of equal to or less than 0.0165, 0.016, 0.015, 0.012, 0.01, 0.0075, 0.005, 0.0025, or lower as determined by a cell killing assay using primary human TRBV9+ T cells, isolated from peripheral blood mononuclear cells (PBMCs), and serially diluted antibodies incubated with the cells for 16 hours at 37°C. In some embodiments, a TCRPV9 targeting molecule provided herein has a human cell killing EC50 of equal to or less than 0.0165 as determined by a cell killing assay using primary human TRBV9+ T cells, isolated from peripheral blood mononuclear cells (PBMCs), and serially diluted antibodies incubated with the cells for 16 hours at 37°C. In some embodiments, increased cell killing corresponds to lower EC50 in a cynomolgus cell killing assay. In some embodiments, a TCRPV9 targeting molecule provided herein has a cynomolgus cell killing EC50 of equal to or less than 0.013, 0.012, 0.01, 0.0075, 0.005, 0.0025, or lower as determined by a cell killing assay using primary cynomolgus TRBV9+ T cells, isolated from peripheral blood mononuclear cells (PBMCs), and serially diluted antibodies incubated with the cells for 16 hours at 37°C. In some embodiments, a TCRPV9 targeting molecule provided herein has a cynomolgus cell killing EC50 of equal to or less than 0.013 as determined by a cell killing assay using primary cynomolgus TRBV9+ T cells, isolated from peripheral blood mononuclear cells (PBMCs), and serially diluted antibodies incubated with the cells for 16 hours at 37°C.I). Additional Antibody Embodiments[000247] The anti-TCRpV9 antibodies described herein can be in any antibody form, including, but not limited to, intact (z.e., full-length) antibodies, antigen-binding fragments thereof (such as Fab, F(ab'), F(ab')2, Fv), single chain antibodies, bi-specific antibodies, or nanobodies. In some embodiments, the anti-TCRpV9 antibody described herein is a scFv. In some embodiments, the anti-TCRpV9 antibody described herein is a scFv-Fab (e.g., scFv7107489fused to a portion of a constant region).[000248] In some embodiments, conservative mutations can be introduced into antibody sequences (e.g., CDRs or framework sequences) at positions where the residues are not likely to be involved in interacting with a target antigen (e.g., TCRPV9), for example, as determined based on a crystal structure. In some embodiments, one, two or more mutations (e.g., amino acid substitutions) are introduced into the Fc region of an anti-TCRpV9 antibody described herein (e.g., in a CH2 domain (residues 231-340 of human IgGl) and / or CH3 domain (residues 341-447 of human IgGl) and / or the hinge region, with numbering according to the Kabat numbering system (e.g., the EU index in Kabat)) to alter one or more functional properties of the antibody, such as serum half-life, complement fixation, Fc receptor binding and / or antigen-dependent cellular cytotoxicity.[000249] In some embodiments, one, two or more mutations (e.g., amino acid substitutions) are introduced into the hinge region of the Fc region (CHI domain) such that the number of cysteine residues in the hinge region are altered (e.g., increased or decreased) as described in, e.g., U.S. Pat. No. 5,677,425. The number of cysteine residues in the hinge region of the CHI domain can be altered to, e.g., facilitate assembly of the light and heavy chains, or to alter (e.g., increase or decrease) the stability of the antibody or to facilitate linker conjugation.[000250] In some embodiments, one, two or more mutations (e.g., amino acid substitutions) are introduced into the Fc region of an antibody described herein (e.g., in a CH2 domain (residues 231-340 of human IgGl) and / or CH3 domain (residues 341-447 of human IgGl) and / or the hinge region, with numbering according to the Kabat numbering system (e.g., the EU index in Kabat)) to increase or decrease the affinity of the antibody for an Fc receptor (e.g., an activated Fc receptor) on the surface of an effector cell. Mutations in the Fc region of an antibody that decrease or increase the affinity of an antibody for an Fc receptor and techniques for introducing such mutations into the Fc receptor or fragment thereof are known to one of skill in the art. Examples of mutations in the Fc receptor of an antibody that can be made to alter the affinity of the antibody for an Fc receptor are described in, e.g., Smith P et al., (2012) PNAS 109: 6181-6186, U.S. Pat. No. 6,737,056, and International Publication Nos. WO 02 / 060919; WO 98 / 23289; and WO 97 / 34631, which are incorporated herein by reference.[000251] In some embodiments, one, two or more amino acid mutations (i.e., substitutions, insertions or deletions) are introduced into an IgG constant domain, or FcRn-binding fragment thereof (preferably an Fc or hinge-Fc domain fragment) to alter (e.g., decrease or increase) half-life of the antibody in vivo. See, e.g., International Publication Nos. WO 710748902 / 060919; WO 98 / 23289; and WO 97 / 34631; and U.S. Pat. Nos. 5,869,046, 6,121,022, 6,277,375 and 6,165,745 for examples of mutations that will alter (e.g., decrease or increase) the half-life of an antibody in vivo.[000252] In some embodiments, one, two or more amino acid mutations (i.e., substitutions, insertions or deletions) are introduced into an IgG constant domain, or FcRn-binding fragment thereof (preferably an Fc or hinge-Fc domain fragment) to increase the half-life of the anti-TCRpV9 antibody in vivo. In some embodiments, one, two or more amino acid mutations (i.e., substitutions, insertions or deletions) are introduced into an IgG constant domain, or FcRn-binding fragment thereof (preferably an Fc or hinge-Fc domain fragment) to increase the half-life of the antibody in vivo. In some embodiments, the antibodies can have one or more amino acid mutations (e.g., substitutions) in the second constant (CH2) domain (residues 231-340 of human IgGl) and / or the third constant (CH3) domain (residues 341-447 of human IgGl), with numbering according to the EU index in Kabat (Kabat E A et al., (1991) supra). In some embodiments, the constant region of the IgGl of an antibody described herein comprises a methionine (M) to tyrosine (Y) substitution in position 252, a serine (S) to threonine (T) substitution in position 254, and a threonine (T) to glutamic acid (E) substitution in position 256, numbered according to the EU index as in Kabat. See U.S. Pat. No. 7,658,921, which is incorporated herein by reference. This type of mutant IgG, referred to as "YTE mutant" has been shown to display fourfold increased half-life as compared to wild- type versions of the same antibody (see Dall'Acqua W F et al., (2006) J Biol Chem 281: 23514-24). In some embodiments, an antibody comprises an IgG constant domain comprising one, two, three or more amino acid substitutions of amino acid residues at positions 251-257, 285-290, 308-314, 385-389, and 428-436, numbered according to the EU index as in Kabat.[000253] In some embodiments, an anti-TCRpV9 antibody of the present disclosure comprises a constant region. In some embodiments, an anti-TCRpV9 antibody comprises an Fc region. In some embodiments, an anti-TCRpV9 antibody comprises an Fc region that has been modified to reduce, prevent, or eliminate Fc-mediated effector functions, such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement fixation, and FcRn-mediated recycling. In some embodiments, an anti-TCRpV9 antibody comprises an afucosylated Fc region. In some embodiments, an anti-TCRpV9 antibody lacks Fc-mediated effector functions. However, in some embodiments, an anti-TCRpV9 antibody comprises one or more Fc regions that support Fc-mediated effector functions, such as antibody-dependent cell-mediated cytotoxicity 7107489(ADCC), antibody-dependent cellular phagocytosis (ADCP), complement fixation, and FcRn-mediated recycling. In some embodiments, an anti-TCRpV9 antibody of the disclosure comprises one or more Fc modifications that alter interactions with FcyRs (e.g., FcyRI, FcyRII, FcyRIII, etc.), such as to increase or decrease affinity and / or binding thereto (e.g., as described in Saxena and Wu, Front Immunol, 2016. 7(580), incorporated herein by reference). Alternatively or in addition, in some embodiments, an anti-TCRpV9 Fc region comprises a structural motif known in the art to alter effector function, such as those described in Damelong et al., Front Immunol, 2024, incorporated herein by reference.[000254] In some embodiments, an anti-TCRpV9 antibody comprises an Fc region that has been modified to enhance antibody-dependent cell-mediated cytotoxicity (ADCC). In some embodiments, an anti-TCRpV9 antibody comprises an Fc region that has been modified to enhance antibody-dependent cellular phagocytosis (ADCP). In some embodiments, an anti-TCRPV9 antibody comprises an Fc region that has been modified to enhance complement fixation. In some embodiments, an anti-TCRpV9 antibody comprises an Fc region that has been modified to enhance complement-dependent cytotoxicity (CDC). In some embodiments, an anti-TCRpV9 antibody comprises an Fc region that has been modified to enhance FcRn-mediated recycling. In some embodiments, an anti-TCRpV9 antibody comprises an Fc region that has been modified to enhance the half-life of the anti-TCRpV9 antibody. In some embodiments, an anti-TCRpV9 antibody comprises an Fc region that has been modified to enhance two or more of (three of more of, four or more of, five or more of, or each of) ADCC, ADCP, complement fixation, CDC, FcRn-mediated recycling, and halflife. In some embodiments, an anti-TCRpV9 antibody comprises an Fc region that has been modified to enhance ADCC and half-life.[000255] In some embodiments, an anti-TCRpV9 antibody comprises an Fc region comprising an amino acid modification (or any combination of amino acid modifications) provided in Table 2 of Damelong et al., Front Immunol, 2024. For example, in some embodiments, an anti-TCRpV9 antibody comprises an Fc region comprising a DLE modification (S239D / A330L / I332E) and / or an YTE modification (as described above).[000256] In some embodiments, an anti-TCRpV9 antibody comprises an Fc region that comprises:a P at position 233;an F at position 234;an A at position 236;an A at position 237;7107489a D at position 238;an A at position 239;an A at position 253;an A at position 254;an A at position 265;an E at position 267;an F at position 268;an A at position 270;an A at position 292;an A, a Q, or a G at position 297;an N at position 298;an A at position 322;a T at position 324;a W at position 326;a Q at position 327;an E or an F at position 328;an A at position 329;a S at position 331;an E at position 332;an A at position 333;an A at position 338;an R at position 345;an A at position 380;a G at position 430;an A at position 433;an A at position 434;aW at position 435;an E at position 439;a K at position 440;a D at position 221 and a C at position 222; a P at position 228 and an E at position 235; an A at position 234 and an A at position 235; an A at position 234 and an E at position 235; an A at position 234 and an A at position 237; 7107489an N at position 236 and a D at position 268;an R at position 236 and an R at position 328;an A at position 236 and an E at position 332;a W at position 236 and an S at position 333;a D at position 239 and an E at position 332;an I at position 247 and a Q at position 339;a Q at position 250 and an L at position 428;a Y at position 252 and a D at position 256;a D at position 256 and a Q at position 307;a D at position 256 and a W at position 307;an I at position 257 and an I at position 311;an E at position 267 and an F at position 328;an F at position 268 and a T at position 324;a G at position 298 and an A at position 299;an A at position 326 and an A at position 333;an M at position 326 and an S at position 333;a W at position 326 and an S at position 333;an S at position 330 and an S at position 331;an A at position 380 and an A at position 434;an L at position 428 and an S at position 434;a K at position 433 and an F at position 434;a P at position 233, a V at position 234, and an A at position 235; an A at position 234, an A at position 235, and an A at position 322; an F at position 234, an E at position 235, and an A at position 322; an F at position 234, a Q at position 235, and a Q at position 322; an A at position 234, an A at position 235, and a G at position 329; an F at position 234, an E at position 235, and an S at position 331; an S at position 234, a T at position 235, and an R at position 236; an A at position 234, an A at position 235, and an A at position 237; an F at position 234, an E at position 235, and an A at position 265; a Y at position 234, a W at position 236, and an A at position 298; an A at position 235, an A at position 237, and an A at position 318; an A at position 236, a D at position 239, and an E at position 332; an A at position 236, an E at position 330, and an E at position 332; 7107489a D at position 239, an A at position 298 and an E at position 332;a D at position 239, an A at position 330, and an E at position 332;a Q at position 250, an L at position 428, and an S at position 434;a Y at position 252, a T at position 254, and an E at position 256;an A at position 253, an A at position 310, and an A at position 435;an I at position 257, an L at position 428, and an S at position 434;an I at position 259, a D at position 315, and a Y at position 434;an E at position 267, an F at position 268, and a T at position 324;a D at position 285, a Q at position 307, and a V at position 378;an A at position 298, an A at position 333, and an A at position 334;an A at position 307, an A at position 380, and A at position 434;a D at position 309, an H at position 311, and an S at position 434;a G at position 327, an S at position 330, and an S at position 331;an E at position 332, an L at position 428, and an S at position 434;an A at position 333, and L at position, 428, and an S at position 434;an R at position 345, a G at position 430, and a Y at position 440;a V at position 376, an L at position 428, and an S at position 434;an A at position 380, an L at position 428, and an S at position 434;an A at position 234, and A at position 235, an A at position 297, and a G at position 329;an A at position 234, an A at position 235, an L at position 428, and an S at position 434;an A at position 236, a D at position 239, and L at position 330, and an E at position 332;a D at position 239, an F at position 268, a T at position 324, and an E at position 332; a D at position 239, an E at position 332, an L at position 428, and an S at position 434;an I at position 257, an I at position 311, an L at position 428, and an S at position 434;an E at position 267, an F at position 328, an L at position 428, and an S at position 434;an F at position 268, a T at position 324, an L at position 428, and an S at position 434;a Q at position 268, an L at position 309, a S at position 330, and an S at position 331; 7107489an A at position 307, an A at position 380, an L at position 428, and an S at position 434;a P at position 233, a V at position 234, an A at position 235, a deletion of the G at position 236, and a K at position 267;a V at position 35, an L at position 243, a P at position 292, an L at position 300, and an L at position 396;an L at position 243, a P at position 292, an L at position 300, an I at position 305, and an L at position 396;an A at position 236, a D at position 239, an E at position 332, an L at position 428, and an S at position 434;an A at position 236, an E at position 267, an F at position 268, a T at position 324, and an E at position 332;a D at position 239, an A at position 298, an E at position 332, an L at position 428, and an S at position 434;a D at position 239, an L at position, 330, an E at position 332, an L at position 428, and an S at position 434;a Y at position 252, a T at position 254, an E at position 256, an L at position 428, and an S at position 434;a Y at position 252, a T at position 254, an E at position 256, a K at position 433, and an F at position 434;an E at position 267, an F at position 268, a T at position 324, an L at position 428, and an S at position 434;a D at position 315, a V at position 330, a D at position 361, a V at position 378 and a Y at position 434;an R at position 345, a G at position 430, a Y at position 440, an L at position 428, an S at position 434;an A at position 236, a D at position 239, an L at position 330, an E at position 332, an L at position 428, and an S at position 434;a Y at position 252, a T at position 254, a Y at position 256, a D at position 239, an L at position 330, and an E at position 332;a D at position 233, a D at position 237, a D at position 238, a D at position, 268, a G at position 271, and an R at position 330;a P at position 233, a V at position 234, an A at position 235, a deletion of the G at position 236, a G at position 327, an S at position 330, and an S at position 331; 7107489an A at position 234, an A at position 235, and A at position 237, an S at position 238, and A at position 268, an S at position 330, and an S at position 331S;a V at position 234, an A at position 237, an S at position 238, an A at position 268, an L at position 309, an S at position 330, and an S at position 331;an A at position 236, an E at position 267, an F at position 268, a T at position 324, an E at position 332, an L at position 428, and an S at position 434; orany combination thereof, with positions determined according to EU numbering.[000257] In some embodiments, an anti-TCRpV9 antibody is engineered to facilitate formation via the knobs-into-holes technique, e.g., to facilitate dimerization. The knobs-into-holes technique may be used, in some embodiments, to produce an anti-TCRpV9 antibody, as discussed in Ridgway JB, et al., 'Knobs-into-holes' engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng 1996; 9:617-21; Atwell S, et al., Stable heterodimers from remodeling the domain interface of a homodimer using a phage display library, J Mol Biol 1997; 270:26-35; and Merchant AM, et al., An efficient route to human bispecific IgG, Nat Biotechnol 1998; 16:677-681, the entire contents of each of which are incorporated herein by reference in their entireties.[000258] In some embodiments, one, two or more amino acid substitutions are introduced into an IgG constant domain Fc region to alter the effector function(s) of the anti-TCRpV9 antibody. The effector ligand to which affinity is altered can be, for example, an Fc receptor or the Cl component of complement. This approach is described in further detail in U.S. Pat. Nos. 5,624,821 and 5,648,260. In some embodiments, the deletion or inactivation (through point mutations or other means) of a constant region domain can reduce Fc receptor binding of the circulating antibody thereby increasing tumor localization. See, e.g., U.S. Pat. Nos. 5,585,097 and 8,591,886 for a description of mutations that delete or inactivate the constant domain and thereby increase tumor localization. In some embodiments, one or more amino acid substitutions may be introduced into the Fc region of an antibody described herein to remove potential glycosylation sites on Fc region, which may reduce Fc receptor binding (see, e.g., Shields R E et al., (2001) J Biol Chem 276: 6591-604).[000259] In some embodiments, one or more amino in the constant region of an anti-TCRPV9 antibody described herein can be replaced with a different amino acid residue such that the antibody has altered Clq binding and / or reduced or abolished complement dependent cytotoxicity (CDC). This approach is described in further detail in U.S. Pat. No. 6,194,551 (Idusogie et al). In some embodiments, one or more amino acid residues in the N-terminal region of the CH2 domain of an antibody described herein are altered to thereby alter the 7107489ability of the antibody to fix complement. This approach is described further in International Publication No. WO 94 / 29351. In some embodiments, the Fc region of an antibody described herein is modified to increase the ability of the antibody to mediate antibody dependent cellular cytotoxicity (ADCC) and / or to increase the affinity of the antibody for an Fey receptor. This approach is described further in International Publication No. WO 00 / 42072.[000260] In some embodiments, the heavy and / or light chain variable domain(s) sequence(s) of the antibodies provided herein can be used to generate, for example, CDR-grafted, chimeric, humanized, or composite human antibodies or antigen-binding fragments, as described elsewhere herein. As understood by one of ordinary skill in the art, any variant, CDR-grafted, chimeric, humanized, or composite antibodies derived from any of the antibodies provided herein may be useful in the compositions and methods described herein and will maintain the ability to specifically bind TCRPV9, such that the variant, CDR-grafted, chimeric, humanized, or composite antibody has at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% or more binding to TCRPV9 relative to the original antibody from which it is derived.[000261] In some embodiments, the antibodies provided herein comprise mutations that confer desirable properties to the antibodies. For example, to avoid potential complications due to Fab-arm exchange, which is known to occur with native IgG4 mAbs, the antibodies provided herein may comprise a stabilizing ‘Adair’ mutation (Angal S., et al., “A single amino acid substitution abolishes the heterogeneity of chimeric mouse / human (IgG4) antibody,” Mol Immunol 30, 105-108; 1993), where serine 228 (EU numbering; residue 241 Kabat numbering) is converted to proline resulting in an IgGl-like hinge sequence.Accordingly, any of the antibodies may include a stabilizing ‘Adair’ mutation.[000262] In some embodiments, an antibody is modified, e.g., modified via glycosylation, phosphorylation, sumoylation, and / or methylation. In some embodiments, an antibody is a glycosylated antibody, which is conjugated to one or more sugar or carbohydrate molecules. In some embodiments, the one or more sugar or carbohydrate molecule are conjugated to the antibody via N-glycosylation, O-glycosylation, C-glycosylation, glypiation (GPI anchor attachment), and / or phosphoglycosylation. In some embodiments, the one or more sugar or carbohydrate molecules are monosaccharides, disaccharides, oligosaccharides, or glycans. In some embodiments, the one or more sugar or carbohydrate molecule is a branched oligosaccharide or a branched glycan. In some embodiments, the one or more sugar or carbohydrate molecule includes a mannose unit, a glucose unit, an N-acetylglucosamine unit, an N-acetylgalactosamine unit, a galactose unit, a fucose unit, or a phospholipid unit. In 7107489some embodiments, there are about 1-10, about 1-5, about 5-10, about 1-4, about 1-3, or about 2 sugar molecules. In some embodiments, a glycosylated antibody is fully or partially glycosylated. In some embodiments, an antibody is glycosylated by chemical reactions or by enzymatic means. In some embodiments, an antibody is glycosylated in vitro or inside a cell, which may optionally be deficient in an enzyme in the N- or O- glycosylation pathway, e.g. a glycosyltransferase. In some embodiments, an antibody is functionalized with sugar or carbohydrate molecules as described in International Patent Application Publication WO2014065661, published on May 1, 2014, entitled, “Modified antibody, antibodyconjugate and process for the preparation thereof’.[000263] In some embodiments, any one of the anti-TCRpV9 antibodies described herein may comprise a signal peptide in the heavy and / or light chain sequence e.g., a N-terminal signal peptide). In some embodiments, the anti-TCRpV9 antibody described herein comprises any one of the VH and VL sequences, any one of the IgG heavy chain and light chain sequences, or any one of the F(ab') heavy chain and light chain sequences described herein, and further comprises a signal peptide (e.g., a N-terminal signal peptide).E. Polynucleotide Encoding an Antibody Disclosed Herein[000264] In some embodiments, the disclosure provides a polynucleotide encoding an anti-TCRPV9 antibody disclosed herein (e.g., an anti-TCRpV9 comprising a VH and / or a VL of Table 16). In some embodiments, a polynucleotide encodes a VH of the disclosure (e.g., a VH provided in Table 16). In some embodiments, a polynucleotide encodes a VL of the disclosure (e.g., a VL provided in Table 16). In some embodiments, a polynucleotide encodes a VH and a VL of the disclosure (e.g., a VH and VL pair provided in Table 16). In some embodiments, a polynucleotide encoding a VH and a VL further encodes a linker and / or a signal peptide (e.g., to direct localization or expression of the VH and the VL). A polynucleotide encoding a VH and / or VL of the disclosure can also further encode a marker (e.g., a fluorescent marker or reporter protein).[000265] In some embodiments, the disclosure provides a polynucleotide encoding a CDR1, a CDR2, and / or a CDR3 of a VH, e.g., as provided in Table 9, and / or a CDR1, a CDR2, and / or a CDR3 of a VL, e.g., as provided in Table 13. Alternatively or an addition, the disclosure provides a polynucleotide encoding a FR1, a FR2, a FR3, and a FR4 of a VH, e.g., as provided in Table 11, and / or a FR1, a FR2, a FR3, and a FR4 of a VL, e.g., as provided in Table 15.7107489F. Cells Expressing an Antibody Disclosed Herein[000266] In some embodiments, the disclosure provides a cell expressing an anti-TCRpV9 antibody disclosed herein (e.g., an anti-TCRpV9 antibody comprising a VH and / or a VL of Table 16). In some embodiments, a cell expresses a VH provided herein (e.g., a VH provided in Table 16). In some embodiments, a cell expresses a VL (e.g., a VL provided in Table 16). In some embodiments, a cell expresses a VH and a VL (e.g., a VH and a VL provided in Table 16). In some embodiments, a cell is transduced or transfected with a polynucleotide encoding a polypeptide provided herein (e.g., a polynucleotide as described in Section III(E) of the present disclosure).G. Methods of Use[000267] In some embodiments, an anti-TCRpV9 antibody of the present disclosure can be used for production a research tool. For example, an anti-TCRpV9 antibody can be used as a tool for assessing a cellular response to the anti-TCRpV9 antibody. In some embodiments, a cellular response to an anti-TCRpV9 antibody of the disclosure comprises a decrease of cellular function. In some embodiments, a cellular response to an anti-TCRpV9 antibody of the disclosure comprises initiation of cell death. In some embodiments, an anti-TCRpV9 antibody can be used to detect a particular cell or cell population, such as a cell that is recognized by the anti-TCRpV9 antibody. In some embodiments, an anti-TCRpV9 antibody disclosed herein can be used for manufacturing a product of interest, such as a therapeutic. For example, an anti-TCRpV9 antibody of the disclosure can be used in the manufacturing of a TCRPV9 targeting molecule. In some embodiments, an anti-TCRpV9 antibody of the disclosure can be used in combination with another therapeutic (e.g., another antibody) to produce a new therapeutic or a new combination therapy. Additional methods of use of anti-TCRPV9 antibodies of the disclosure are described elsewhere herein.IV. Preparation of Polypeptides and Anti-TCRpV9 Antibodies[000268] Antibodies capable of binding TCRPV9 and polypeptides as described herein can be made by any method known in the art. See, for example, Harlow and Lane, (1998) Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, New York.[000269] In some embodiments, antibodies specific to a target antigen (e.g., TCRPV9) can be made by the conventional hybridoma technology. The full-length target antigen or a fragment thereof, optionally coupled to a carrier protein such as KLH, can be used to immunize a host animal for generating antibodies binding to that antigen. The route and schedule of7107489immunization of the host animal are generally in keeping with established and conventional techniques for antibody stimulation and production, as further described herein. General techniques for production of mouse, humanized, and human antibodies are known in the art and are described herein. It is contemplated that any mammalian subject including humans or antibody producing cells therefrom can be manipulated to serve as the basis for production of mammalian, including human hybridoma cell lines. Typically, the host animal is inoculated intraperitoneally, intramuscularly, orally, subcutaneously, intraplantar, and / or intradermally with an amount of immunogen, including as described herein.[000270] If desired, an antibody (monoclonal or polyclonal) of interest (e.g., produced by a hybridoma) or polypeptide may be sequenced and the polynucleotide sequence may then be cloned into a vector for expression or propagation. The sequence encoding the antibody or polypeptide of interest may be maintained in vector in a host cell and the host cell can then be expanded and frozen for future use. In an alternative, the polynucleotide sequence may be used for genetic manipulation to “humanize” the antibody or polypeptide or to improve the affinity (affinity maturation), or other characteristics of the antibody. For example, the constant region of an antibody may be engineered to more closely resemble human constant regions to avoid immune response if the antibody is used in clinical trials and treatments in humans. It may be desirable to genetically manipulate the antibody sequence to obtain greater affinity to the target antigen and greater efficacy. It will be apparent to one of skill in the art that one or more polynucleotide changes can be made to the antibody and still maintain its binding specificity to the target antigen.[000271] In other embodiments, fully human antibodies or polypeptides can be obtained by using commercially available mice that have been engineered to express specific human immunoglobulin proteins or other human proteins. Transgenic animals that are designed to produce a more desirable (e.g., fully human antibodies or human polypeptides) or more robust immune response may also be used for generation of humanized or human antibodies. Examples of such technology are XenomouseRTM from Amgen, Inc. (Fremont, CA) and HuMAb-MouseRTM and TC MouseTM from Medarex, Inc. (Princeton, NJ) or H2L2 mice from Harbour Antibodies BV (Holland). In another alternative, antibodies may be made recombinantly by phage display or yeast technology. See, for example, U.S. Pat. Nos.5,565,332; 5,580,717; 5,733,743; and 6,265,150; and Winter etal., (1994) Annu. Rev.Immunol. 12:433-455. Alternatively, the phage display technology (McCafferty et al., (1990) Nature 348:552-553) can be used to produce human antibodies and antibody fragments in vitro, from immunoglobulin variable (V) domain gene repertoires from unimmunized donors.7107489[000272] Antigen-binding fragments of an intact antibody (full-length antibody) or fragments of a polypeptide of the disclosure can be prepared via routine methods. For example, F(ab')2 fragments can be produced by pepsin digestion of an antibody molecule, and Fab fragments that can be generated by reducing the disulfide bridges of F(ab')2 fragments. Genetically engineered antibodies, such as humanized antibodies, chimeric antibodies, single-chain antibodies, and bi-specific antibodies, can be produced via, e.g., conventional recombinant technology. In one example, DNA encoding a polypeptide or a monoclonal antibodies specific to a target antigen can be readily isolated and sequenced using conventional procedures e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the monoclonal antibodies). The hybridoma cells serve as a preferred source of such DNA. Once isolated, the DNA may be placed into one or more expression vectors, which are then transfected into host cells such as E. coli cells, simian COS cells, Chinese hamster ovary (CHO) cells, human HEK293 cells, or myeloma cells that do not otherwise produce immunoglobulin protein or polypeptides of the disclosure, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. See, e.g., PCT Publication No. WO 87 / 04462. The DNA can then be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences, Morrison et al., (1984) Proc. Nat. Acad. Sci. 81:6851, or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. In that manner, genetically engineered antibodies, such as “chimeric” or “hybrid” antibodies; can be prepared that have the binding specificity of a target antigen.[000273] A single-chain antibody can be prepared via recombinant technology by linking a nucleotide sequence coding for a heavy chain variable region and a nucleotide sequence coding for a light chain variable region. Preferably, a flexible linker is incorporated between the two variable regions.[000274] Alternatively, techniques described for the production of single chain antibodies (U.S. Patent Nos. 4,946,778 and 4,704,692) can be adapted to produce a phage or yeast scFv library and scFv clones specific to TCR[3V9 can be identified from the library following routine procedures. Positive clones can be subjected to further screening to identify those that has high TCR[3V9 binding affinity.[000275] Antibodies or polypeptides obtained following a method known in the art and described herein can be characterized using methods well known in the art. For example, one method is to identify the epitope to which the antigen binds, or “epitope mapping.” There are 7107489many methods known in the art for mapping and characterizing the location of epitopes or substrate domains on proteins, including solving the crystal structure of an antibody-antigen complex, competition assays, gene fragment expression assays, and synthetic peptide-based assays, as described, for example, in Chapter 11 of Harlow and Lane, Using Antibodies, a Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1999. In one example, epitope mapping can be accomplished use H / D-Ex (hydrogen deuterium exchange) coupled with proteolysis and mass spectrometry. In an additional example, epitope mapping can be used to determine the sequence to which an antibody binds. The epitope can be a linear epitope, i.e., contained in a single stretch of amino acids, or a conformational epitope formed by a three-dimensional interaction of amino acids that may not necessarily be contained in a single stretch (primary structure linear sequence). Peptides of varying lengths (e.g., at least 4-6 amino acids long) can be isolated or synthesized (e.g., recombinantly) and used for binding assays with an antibody. In another example, the epitope to which the antibody binds can be determined in a systematic screening by using overlapping peptides derived from the target antigen sequence and determining binding by the antibody. According to the gene fragment expression assays, the open reading frame encoding the target antigen is fragmented either randomly or by specific genetic constructions and the reactivity of the expressed fragments of the antigen with the antibody to be tested is determined. The gene fragments may, for example, be produced by PCR and then transcribed and translated into protein in vitro, in the presence of radioactive amino acids. The binding of the antibody to the radioactively labeled antigen fragments is then determined by immunoprecipitation and gel electrophoresis. Certain epitopes can also be identified by using large libraries of random peptide sequences displayed on the surface of phage particles (phage libraries). Alternatively, a defined library of overlapping peptide fragments can be tested for binding to the test antibody in simple binding assays. In an additional example, mutagenesis of an antigen binding domain, domain swapping experiments and alanine scanning mutagenesis can be performed to identify residues required, sufficient, and / or necessary for epitope binding. Alternatively, competition assays can be performed using other antibodies known to bind to the same antigen to determine whether an antibody binds to the same epitope as the other antibodies. Competition assays are well known to those of skill in the art.[000276] In some examples, an anti-TCRpV9 antibody or polypeptide is prepared by recombinant technology as exemplified below. Nucleic acids encoding the heavy and light chain of an anti-TCRpV9 antibody or polypeptide as described herein can be cloned into one expression vector, each nucleotide sequence being in operable linkage to a suitable promoter.7107489In one example, each of the nucleotide sequences encoding the heavy chain and light chain or the first polypeptide and the second polypeptide (e.g., in a polypeptide pair of Table 7) is in operable linkage to a distinct promoter. Alternatively, the nucleotide sequences encoding the heavy chain and the light chain can be in operable linkage with a single promoter, such that both heavy and light chains are expressed from the same promoter. When necessary, an internal ribosomal entry site (IRES) can be inserted between the heavy chain and light chain encoding sequences.[000277] In some examples, the nucleotide sequences encoding the two chains of the antibody are cloned into two vectors, which can be introduced into the same or different cells. When the two chains are expressed in different cells, each of them can be isolated from the host cells expressing such and the isolated heavy chains and light chains can be mixed and incubated under suitable conditions allowing for the formation of the antibody. In some embodiments, the disclosure provides a vector comprising a polynucleotide encoding a VH and / or a VL provided herein (e.g., a VH and / or VL of Table 16). In some embodiments, the disclosure provides a vector comprising a polynucleotide encoding a polynucleotide provided herein (e.g. a first polynucleotide and / or a second polynucleotide of Table 7).[000278] Generally, a nucleic acid sequence encoding one or all chains of an antibody or a polypeptide (e.g. a first polypeptide and / or a second polypeptide) can be cloned into a suitable expression vector in operable linkage with a suitable promoter using methods known in the art. For example, the nucleotide sequence and vector can be contacted, under suitable conditions, with a restriction enzyme to create complementary ends on each molecule that can pair with each other and be joined together with a ligase. Alternatively, synthetic nucleic acid linkers can be ligated to the termini of a gene. These synthetic linkers contain nucleic acid sequences that correspond to a particular restriction site in the vector. The selection of expression vectors / promoter would depend on the type of host cells for use in producing the antibodies.[000279] In some embodiments, the disclosure provides a vector comprising a nucleic acid sequence encoding a polypeptide, a heavy chain variable (VH) domain, and / or a light chain variable (VL) domain provided herein.[000280] In some embodiments, a vector comprises a nucleic acid encoding one or more polypeptides selected from Table 3. In some embodiments, a vector comprises a nucleic acid encoding one or more polypeptides selected from Table 6. In some embodiments, a vector comprises a nucleic acid encoding one or more polypeptide pairs selected from Table 7.[000281] In some embodiments, a vector comprises a nucleic acid encoding one or more VH 7107489domains comprising one or more CDRs selected from Table 9. In some embodiments, a vector comprises a nucleic acid encoding one or more VH domains comprising one or more framework regions (FRs) selected from Table 11.[000282] In some embodiments, a vector comprises a nucleic acid encoding one or more VL domains comprising one or more CDRs selected from Table 13. In some embodiments, a vector comprises a nucleic acid encoding one or more VL domains comprising one or more FR regions selected from Table 15.[000283] A variety of promoters can be used for expression of the antibodies described herein, including, but not limited to, cytomegalovirus (CMV) intermediate early promoter, a viral LTR such as the Rous sarcoma virus LTR, HIV-LTR, HTLV-1 LTR, the simian virus 40 (SV40) early promoter, E. coli lac UV promoter, and the herpes simplex tk virus promoter.[000284] Regulatable promoters can also be used. Such regulatable promoters include those using the lac repressor from E. coli as a transcription modulator to regulate transcription from lac operator bearing mammalian cell promoters (Brown, M. et al., Cell, 49:603-612 (1987)), those using the tetracycline repressor (tetR) (Gossen, M., and Bujard, H., Proc. Natl. Acad. Sci. USA 89:5547-555115 (1992); Yao, F. et al., Human Gene Therapy, 9:1939-1950 (1998); Shockelt, P., et al., Proc. Natl. Acad. Sci. USA, 92:6522-6526 (1995)). Other systems include FK506 dimer, VP 16 or p65 using astradiol, RU486, diphenol murislerone, or rapamycin. Inducible systems are available from Invitrogen, Clontech and Ariad, among others.[000285] Regulatable promoters that include a repressor with the operon can be used. In one embodiment, the lac repressor from E. coli can function as a transcriptional modulator to regulate transcription from lac operator-bearing mammalian cell promoters [[M. Brown et al., Cell, 49:603-612 (1987)]]; Gossen and Bujard (1992); [[M. Gossen etal., Natl. Acad. Sci. USA, 89:5547-5551(1992)]] combined the tetracycline repressor (tetR) with the transcription activator (VP 16) to create a tetR-mammalian cell transcription activator fusion protein, tTa (tetR- VP 16), with the tetO bearing minimal promoter derived from the human cytomegalovirus (hCMV) promoter to create a tetR-tet operator system to control gene expression in mammalian cells. In one embodiment, a tetracycline inducible switch is used. The tetracycline repressor (tetR) alone, rather than the tetR-mammalian cell transcription factor fusion derivatives can function as potent trans-modulator to regulate gene expression in mammalian cells when the tetracycline operator is properly positioned downstream for the TATA element of the CMVIE promoter (Yao et al., Human Gene Therapy). One particular advantage of this tetracycline inducible switch is that it does not require the use of a7107489tetracycline repressor-mammalian cells transactivator or repressor fusion protein, which in some instances can be toxic to cells (Gossen 5 et al., Natl. Acad. Sci. USA, 89:5547-5551 (1992); Shockett etal., Proc. Natl. Acad. Sci. USA, 92:6522-6526 (1995)), to achieve its regulatable effects.[000286] Additionally, the vector can contain, for example, some or all of the following: a selectable marker gene, such as the neomycin gene for selection of stable or transient transfectants in mammalian cells; enhancer / promoter sequences from the immediate early gene of human CMV for high levels of transcription; transcription termination and RNA processing signals from SV40 for mRNA stability; SV40 polyoma origins of replication and ColEl for proper episomal replication; internal ribosome binding sites (IRESes), versatile multiple cloning sites; and T7 and SP6 RNA promoters for in vitro transcription of sense and antisense RNA. Suitable vectors and methods for producing vectors containing transgenes are well known and available in the art. Examples of polyadenylation signals useful to practice the methods described herein include, but are not limited to, human collagen I polyadenylation signal, human collagen II polyadenylation signal, and SV40 polyadenylation signal.[000287] One or more vectors (e.g., expression vectors) comprising nucleic acids encoding any of the antibodies may be introduced into suitable host cells for producing the antibodies. Non-limiting examples of the host cells include Chinese hamster ovary (CHO) cells, dhfr-CHO cell, human embryonic kidney (HEK)-293 cells, verda reno (VERO) cells, nonsecreting null (NS0) cells, human embryonic retinal (PER.C6) cells, Sp2 / 0 cells, baby hamster kidney (BHK) cells, Madin-Darby Canine Kidney (MDCK) cells, Madin-Darby Bovine Kidney (MDBK) cells, and monkey kidney CV1 line transformed by SV40 (COS) cells. In some embodiments, the host cell expressing the anti-TCRpV9 antibodies are CHO cells. The host cells can be cultured under suitable conditions for expression of the antibody or any polypeptide chain thereof. Such antibodies or polypeptide chains thereof can be recovered by the cultured cells (e.g., from the cells or the culture supernatant) via a conventional method, e.g., affinity purification. If necessary, polypeptide chains of the antibody can be incubated under suitable conditions for a suitable period of time allowing for production of the antibody. In some embodiments, the host cell comprises the nucleic acid encoding the heavy chain of the anti-TCRpV9 antibody. In some embodiments, the host cell comprises the nucleic acid encoding the light chain of the anti-TCRpV9 antibody. In some embodiments, the host cell comprises the nucleic acid encoding the heavy chain and the nucleic acid encoding the light chain.7107489[000288] In some embodiments, methods for preparing an antibody described herein involve a recombinant expression vector that encodes both the heavy chain and the light chain of an anti-TCRpV9 antibody, as also described herein. The recombinant expression vector can be introduced into a suitable host cell (e.g., a dhfr- CHO cell) by a conventional method, e.g., calcium phosphate mediated transfection. Positive transformant host cells can be selected and cultured under suitable conditions allowing for the expression of the two polypeptide chains that form the antibody, which can be recovered from the cells or from the culture medium. When necessary, the two chains recovered from the host cells can be incubated under suitable conditions allowing for the formation of the antibody.[000289] In one example, two recombinant expression vectors are provided, one encoding the heavy chain of the anti-TCRpV9 antibody and the other encoding the light chain of the anti-TCRPV9 antibody. Both of the two recombinant expression vectors can be introduced into a suitable host cell e.g., dhfr- CHO cell) by a conventional method, e.g., calcium phosphate-mediated transfection.[000290] Alternatively, each of the expression vectors can be introduced into a suitable host cells. Positive transformants can be selected and cultured under suitable conditions allowing for the expression of the polypeptide chains of the antibody. When the two expression vectors are introduced into the same host cells, the antibody produced therein can be recovered from the host cells or from the culture medium. If necessary, the polypeptide chains can be recovered from the host cells or from the culture medium and then incubated under suitable conditions allowing for formation of the antibody. When the two expression vectors are introduced into different host cells, each of them can be recovered from the corresponding host cells or from the corresponding culture media. The two polypeptide chains can then be incubated under suitable conditions for formation of the antibody.[000291] Standard molecular biology techniques are used to prepare the recombinant expression vector, transfect the host cells, select for transformants, culture the host cells and recovery of the antibodies from the culture medium. For example, some antibodies can be isolated by affinity chromatography with a Protein A or Protein G coupled matrix.[000292] Any of the nucleic acids encoding the heavy chain, the light chain, or both of an anti-TCRpV9 antibody as described herein, vectors (e.g., expression vectors) containing such; and host cells comprising the vectors are within the scope of the present disclosure.[000293] In some embodiments, the antibodies described herein is used to modulate the activity or function of at least one gene, protein, and / or nucleic acid. In some embodiments, the molecular payload is responsible for the modulation of a gene, protein, and / or nucleic 7107489acids. A molecular payload may be a small molecule, protein, nucleic acid, oligonucleotide, or any molecular entity capable of modulating the activity or function of a gene, protein, and / or nucleic acid in a cell.V. Pharmaceutical Composition[000294] The antibodies, as well as the encoding nucleic acids or nucleic acid sets, vectors comprising such, or host cells comprising the vectors, as described herein can be mixed with a pharmaceutically acceptable carrier (excipient) to form a pharmaceutical composition for use in treating a target disease. “Acceptable” means that the carrier must be compatible with the active ingredient of the composition (and preferably, capable of stabilizing the active ingredient) and not deleterious to the subject to be treated. Pharmaceutically acceptable excipients (carriers) including buffers, which are well known in the art. See, e.g., Remington: The Science and Practice of Pharmacy 20th Ed. (2000) Lippincott Williams and Wilkins, Ed. K. E. Hoover.[000295] The anti-TCRpV9 antibody containing pharmaceutical composition disclosed herein may further comprise a suitable buffer agent. A buffer agent is a weak acid or base used to maintain the pH of a solution near a chosen value after the addition of another acid or base. In some examples, the buffer agent disclosed herein can be a buffer agent capable of maintaining physiological pH despite changes in carbon dioxide concentration (produced by cellular respiration). Exemplary buffer agents include, but are not limited to a HEPES (4-(2-hy droxy ethyl) -1 -piperazineethanesulfonic acid) buffer, Dulbecco's phosphate-buffered saline (DPBS) buffer, or Phosphate-buffered Saline (PBS) buffer. Such buffers may comprise disodium hydrogen phosphate and sodium chloride, or potassium dihydrogen phosphate and potassium chloride.[000296] In some embodiments, the buffer agent in the pharmaceutical composition described herein may maintain a pH value of about 5-8. For example, the pH of the pharmaceutical composition can be about 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or 8.0. In other examples, the pharmaceutical composition may have a pH value lower than 7, for example, about 7, 6.8, 6.5, 6.3, 6, 5.8, 5.5, 5.3, or 5.[000297] The pharmaceutical composition described herein comprises one or more suitable salts. A salt is an ionic compound that can be formed by the neutralization reaction of an acid and a base. (Skoog, D.A; West, D.M.; Holler, J.F.; Crouch, S.R. (2004). “chapters 14-16”. Fundamentals of Analytical Chemistry (8th ed.)). Salts are composed of related numbers of cations (positively charged ions) and anions (negative ions) so that the product is electrically 7107489neutral (without a net charge).[000298] In some embodiments, the pharmaceutical compositions can comprise pharmaceutically acceptable carriers, excipients, or stabilizers in the form of lyophilized formulations or aqueous solutions. (Remington: The Science and Practice of Pharmacy 20th Ed. (2000) Lippincott Williams and Wilkins, Ed. K. E. Hoover). In some embodiments, the pharmaceutical composition can be formulated for intravenous injection. In some embodiments, the pharmaceutical composition can be formulated for subcutaneous injection.[000299] The pharmaceutical compositions to be used for in vivo administration must be sterile. This is readily accomplished by, for example, filtration through sterile filtration membranes. Therapeutic antibody compositions are generally placed into a container having a sterile access port, for example, an intravenous or subcutaneous solution bag or vial having a stopper pierceable by a hypodermic injection needle.VI. Methods of Treatment[000300] Aspects of the disclosure relate to compositions and methods for treating autoimmune disorders, or symptoms of said disorders, in a subject. In some embodiments, an anti-TCRpV9 antibody provided herein is used to treat an autoimmune disorder. In some embodiments, an anti-TCRpV9 antibody is used to treat a T cell-mediated autoimmune disorder. In some embodiments, an anti-TCRpV9 antibody is used to treat an autoimmune disorder associated with TCRpV9-positive T cells.[000301] Although TCRPV9 is not among the most commonly-expressed P-chain motifs, it is typically detectable in the TCR repertoire of T cells isolated from human subjects. TCRPV9-positive T cells are not biased towards differentiation into particular T effector phenotype (e.g., CD8+cytotoxic lymphocytes, CD4+T helper 1 [THI] cells, CD4+T helper 2 [TH2] cells, CD4+T helper 17 [TH17] cells, etc.) (Britanova et al., Nat Med. 2023. 29(11): 2731-2736). Accordingly, targeting of TCRpV9-positive T cells (e.g., using an anti-TCRpV9 antibody provided herein) can be more effective than targeting effector cytokines produced by TCRpV9-positive T cells alone, which vary depending on the phenotype of the T cell.[000302] In some cases, the pathogenicity of TCRpV9-positive T cells has been associated with HLA-B*27 (also called HLA-B27 and HLA-B27, subtypes B*2701-2759), a particular variant of the human leukocyte antigen (HLA) B gene, which encodes a class I surface molecule. Class I HLA molecules (HLA molecules corresponding to major histocompatibility complex, MHC, class I) complex with antigen (e.g., microbial antigen or cancer-associate antigen) on the surface of antigen-presenting cells for recognition by and subsequent7107489activation of CD8+ T cells that possess a TCR specific for that antigen. The combination of the HLA-B*27 variant and TCRpV9-positive T cells may therefore contribute to the pathogenesis of autoreactive TCRpV9-positive T cells. For example, nine out of ten individuals with ankylosing spondylitis (AS), an autoimmune condition associated with TCRpV9-positive T cells, are positive for HLA-B*27, and half of individuals with psoriatic arthritis, another autoimmune condition associated with TCRpV9-positive T cells, are positive for HLA-B*27. Other autoimmune conditions associated with TCRpV9-positive T cells are not associated with the HLA-B*27 variant. Thus, while the class I variant HLA-B*27 is associated with some autoimmune conditions, it is not the sole mediator, and targeting TCRpV9-positive T cells (e.g., using an anti-TCRpV9 antibody provided herein) can be useful in treating or ameliorating such autoimmune conditions, in lieu of or in addition to existing therapies.[000303] Any suitable method can be used to determine whether a subject has TCRPV9-positive T cells. In some embodiments, determining whether a subject has TCRpV9-positive T cells comprises obtaining a sample from the subject. In some embodiments, a sample is a biopsy. In some embodiments, a sample is a tissue sample. In some embodiments, a sample is a blood sample. In some embodiments, determining whether a subject has TCRpV9-positive T cells comprises assaying a sample for TCRPV9 expression. Methods of assaying a sample for TCRPV9 are known in the art, including, but not limited to, flow cytometry, Western blot, enzyme-linked immunosorbent assay (ELISA), mass spectrometry, immunoprecipitation, fluorescent microscopy, and / or protein arrays. In some embodiments, determining whether a sample has TCRpV9-positive T cells comprises isolating T cells from a sample prior and assaying the isolated T cells for TCRPV9 expression.[000304] Some autoimmune conditions associated with TCRpV9-positive T cells, and therefore suitable for treatment with the anti-TCRpV9 antibodies provided herein include:[000305] Ankylosing spondylitis (AS, also called axial spondyloarthritis), a relatively common chronic inflammatory disease that primarily affects the spine. Symptoms include persistent back pain and stiffness, as well as pain and stiffness in other joints, reduced range of motion in the spine, fatigue, and digestive problems. T cells expressing TCRPV9 are often enriched in the peripheral blood and inflamed tissues of individuals with AS, and T cells are known to contribute to the pathogenesis of the disease (see, e.g., Britanova et al., 2023). In some embodiments, the disclosure provides a method of treating a subject having or suspected of having ankylosing spondylitis, the method comprising administering an anti-TCRPV9 antibody provided herein to the subject. In some embodiments, administering an 7107489anti-TCRpV9 antibody provided herein to a subject having ankylosing spondylitis attenuates the symptoms associated with ankylosing spondylitis, including joint pain and stiffness, fatigue, and / or digestive problems. Any suitable diagnostic test or tests can be used to determine whether a subject has or is suspected of having ankylosing spondylitis, including but not limited to physical exams to determine spinal range of motion, X-rays, magnetic resonance imaging (MRI), and / or blood tests.[000306] Acute anterior uveitis, AAU, is an inflammatory condition associated with ankylosing spondylitis, inflammatory bowel disease, and other autoimmune conditions, that affects the iris and ciliary body of the eye. Symptoms of AAU include pain, redness, blurred vision, sensitivity to light, and ciliary flush. Subjects having AAU have been observed to have an enrichment in TCRpV9-positive T cells (see Britanova et al., 2023). In some embodiments, the disclosure provides a method of treating a subject having or suspected of having acute anterior uveitis, the method comprising administering an anti-TCRpV9 antibody provided herein to the subject. In some embodiments, administering an anti-TCRpV9 antibody provided herein to a subject having acute anterior uveitis attenuates the symptoms associated with acute anterior uveitis, including pain, redness, blurred vision, sensitivity to light, and / or ciliary flush. Any suitable diagnostic test or tests can be used to determine whether a subject has or is suspected of having acute anterior uveitis, including but not limited to slit lamp examinations, visual acuity tests, and / or blood tests.[000307] Celiac disease, a T cell-mediated autoimmune disorder in which the immune system causes damage (e.g., via release of inflammatory mediators) to the small intestine upon exposure to gluten protein, found in wheat, rye, and barley. Symptoms of celiac disease include diarrhea, bloating, abdominal pain, nausea, vomiting, anemia, fatigue, joint pain, and skin rashes upon exposure to gluten. TCRpV9-positive T cells have been identified as key drivers of pathogenesis in celiac disease (see, e.g., Broughton et al., Immunity. 2012. 37(4): 611-621). In some embodiments, the disclosure provides a method of treating a subject having or suspected of having celiac disease, the method comprising administering an anti-TCRPV9 antibody provided herein to the subject. In some embodiments, administering an anti-TCRpV9 antibody provided herein to a subject having celiac disease attenuates the symptoms associated with celiac disease, including diarrhea, bloating, abdominal pain, nausea, vomiting, anemia, fatigue, joint pain, and / or skin rashes. Any suitable diagnostic test or tests can be used to determine whether a subject has or is suspected of having celiac disease, including but not limited to blood tests (e.g., for celiac-associated antibodies, such as7107489tissue transglutaminase (tTG) antibodies and endomysial (EMA) antibodies), intestinal biopsy, genetic testing, and / or nutritional / dietary testing.[000308] Psoriatic arthritis, an inflammatory autoimmune disorders that affects some individuals having psoriasis, a skin condition that causes red, scaly rashes. Symptoms of psoriatic arthritis include joint pain, stiffness, swelling, skin rash, red eyes, and nail discoloration. TCRpV9-positive CD8+T cells have been associated with the pathogenesis of psoriatic arthritis (see Britanova et al. 2023). In some embodiments, the disclosure provides a method of treating a subject having or suspected of having psoriatic arthritis, the method comprising administering an anti-TCRpV9 antibody provided herein to the subject. In some embodiments, administering an anti-TCRpV9 antibody provided herein to a subject having psoriatic arthritis attenuates the symptoms associated with psoriatic arthritis, including joint pain, stiffness, swelling, skin rash, red eyes, and / or nail discoloration. Any suitable diagnostic test or tests can be used to determine whether a subject has or is suspected of having psoriatic arthritis, including but not limited to blood tests (e.g., for the presence of antibodies associated with non-psoriatic arthritis), X-rays, computed tomography (CT) scan, ultrasound, MRI, and / or skin biopsy.[000309] Multiple sclerosis, MS, a chronic, degenerative autoimmune disease affecting the central nervous system. A variety of symptoms are associated with MS, including but not limited to numbness or tingling, weakness, paralysis, pain, difficulty with balance, muscle stiffness, muscle spasms, difficulty walking, fatigue, difficulty concentrating, confusion, disorientation, blurred vision, double vision, loss of vision, eye pain, difficulty swallowing, and difficulty speaking. The pathogenesis of multiple sclerosis is driven in large part by autoreactive CD8+T cells that attack myelin, the fatty layer that sheathes axons of nerve cells. The destruction of myelin results in inflammation and impaired or inhibited neuronal signaling. An increase in the frequency of TCRpV9-positive CD8+ T cells has been observed in individuals suffering from MS across stages of the disease (see, e.g., Monteiro et al., Autoimmunity. 1996. 23(2): 127-138; Gran et al., J Neuroimmunol. 1998. 85(1): 22-32). In some embodiments, the disclosure provides a method of treating a subject having or suspected of having multiple sclerosis, the method comprising administering an anti-TCRPV9 antibody provided herein to the subject. In some embodiments, administering an anti-TCRpV9 antibody provided herein to a subject having multiple sclerosis attenuates the symptoms associated with multiple sclerosis, including numbness or tingling, weakness, paralysis, pain, difficulty with balance, muscle stiffness, muscle spasms, difficulty walking, fatigue, difficulty concentrating, confusion, disorientation, blurred vision, double vision, loss 7107489of vision, eye pain, difficulty swallowing, and / or difficulty speaking. Any suitable diagnostic test or tests can be used to determine whether a subject has or is suspected of having multiple sclerosis, including but not limited to MRI, spinal tap, evoked nerve potential tests, blood tests, neuropsychological testing, and / or optical coherence tomography.[000310] Inflammatory bowel disease, IBD, a group of chronic, autoimmune conditions that includes ulcerative colitis and Crohn’s disease. Ulcerative colitis is characterized by inflammation that affects only the colon (large intestine), while inflammation associated with Crohn’s disease can occur anywhere in the digestive tract (including, e.g., the mouth).Symptoms of IBD include abdominal pain and cramping, diarrhea, constipation, rectal bleeding, fatigue, weight loss, fever, nausea, vomiting, skin rashes, eye inflammation, and joint pain. Autoreactive T cells have been identified in the inflamed tissue of individuals with inflammatory bowel disease, and there is some suggestion that TCRpV9-positive T cells may contribute to the pathogenesis of IBD, due to the association of the class I variant HLA-B*27 with IBD and the TCRPV9 motif characteristic of individuals carrying the HLA-B*27 variant (see, Britanova et al., 2023). In some embodiments, the disclosure provides a method of treating a subject having or suspected of having inflammatory bowel disease, the method comprising administering an anti-TCRpV9 antibody provided herein to the subject. In some embodiments, administering an anti-TCRpV9 antibody provided herein to a subject having inflammatory bowel disease attenuates the symptoms associated with inflammatory bowel disease, including abdominal pain and cramping, diarrhea, constipation, rectal bleeding, fatigue, weight loss, fever, nausea, vomiting, skin rashes, eye inflammation, and / or joint pain. Any suitable diagnostic test or tests can be used to determine whether a subject has or is suspected of having inflammatory bowel disease, including but not limited to endoscopy (e.g., colonoscopy, flexible sigmoidoscopy, sigmoidoscopy, and / or upper endoscopy), blood tests, stool tests, CT scans, and / or MRI scans.[000311] Determination of whether an amount of the antibody (e.g., anti-TCRpV9 antibody) achieved the therapeutic effect would be evident to one of skill in the art based on the teachings provided herein. Effective amounts vary, as recognized by those skilled in the art, depending on the particular condition being treated, the severity of the condition, the individual patient parameters including age, physical condition, size, gender and weight, the duration of the treatment, the nature of concurrent therapy (if any), the specific route of administration and like factors within the knowledge and expertise of the health practitioner. In some embodiments, administration comprises subcutaneous administration. The particular dosage regimen, i.e., dose, timing and repetition, used in the method described herein will 7107489depend on the particular subject and that subject's medical history, as discussed herein.[000312] Empirical considerations, such as time to maximum effect, the half-life, and / or time above a specific concentration generally will contribute to the determination of the dosage. For example, antibodies that are compatible with the human immune system, such as humanized antibodies or fully human antibodies, may be used to prolong half-life of the antibody and to prevent the antibody being attacked by the host's immune system. Other reasons for dose-adjusting include differences in pharmacokinetics or pharmacodynamic response driven by sex, age, individual response, polymorphisms on the antibody target and / or receptors involved in antibody clearance. Frequency of administration may be determined and adjusted over the course of therapy, and is generally, but not necessarily, based on treatment and / or suppression and / or amelioration and / or delay of a target disease / disorder. Alternatively, sustained continuous release formulations of an antibody may be appropriate. Various formulations and devices for achieving sustained release are known in the art.[000313] Dosing frequencies may vary in accordance with the claimed methods. In some embodiments, a composition may be administered once. In some embodiments, a composition will be administered on multiple occasions. In some embodiments, dosing frequency is every week, every 2 weeks, every 3 weeks, every 4 weeks, every 5 weeks, every 6 weeks, every 7 weeks, every 8 weeks, every 9 weeks, or every 10 weeks; or once every month, every 2 months, or every 3 months, or longer. In some embodiments, a composition will be administered daily, biweekly, weekly, bimonthly, monthly, or at any time interval that provide suitable (e.g., maximal) efficacy while minimizing safety risks to the subject.Generally, the efficacy and the treatment and safety risks may be monitored throughout the course of treatment.[000314] In some embodiments, a subject may be administered a composition provided herein (e.g., an anti-TCRpV9 antibody) at one or more intervals during a set period of time. In some cases, periods of time during which a subject is administered a composition at one or more intervals may be separated by periods of time in which the subject is not administered the composition. In some embodiments, the relative durations of respective periods of time may depend on the subject’s response to treatment or severity of disease or both and / or may be determined based on the judgment of a treating physician. For example, in some embodiments, the frequency of administration may be increased to alleviate symptoms in the case of severe disease or disease flare-ups. The frequency of administration may also be decreased, for example, titrated down to the lowest efficacious dose.7107489[000315] In some embodiments, an antibody can be administered parenterally. For example, a parenterally administered composition may be administered by subcutaneous, intracutaneous, intravenous, intraperitoneal, intratumor, intramuscular, intraarticular, intraarterial, or infusion techniques. In addition, it can be administered to the subject via injectable depot routes of administration such as using 1-, 3-, or 6-month depot injectable or biodegradable materials and methods.[000316] In some embodiments, an antibody (e.g., an anti-TCRpV9 antibody) is administered intravenously. In some embodiments, an antibody (e.g., an anti-TCRpV9 antibody) is administered subcutaneously. In some embodiments, subcutaneous administration of an ani-TCRPV9 antibody results in similar bioavailability compared to intravenous administration of the same antibody at the same dose.[000317] For intravenous injection, water soluble antibodies can be administered by the drip method, whereby a pharmaceutical formulation containing the antibody and a physiologically acceptable excipient is infused. Physiologically acceptable excipients may include, for example, 5% dextrose, 0.9% saline. Ringer’s solution or other suitable excipients. Other injectable compositions may contain various carriers such as vegetable oils, dimethylactamide, dimethyformamide, ethyl lactate, ethyl carbonate, isopropyl myristate, ethanol, and polyols (glycerol, propylene glycol, liquid polyethylene glycol, and the like). In some cases, preparations, e.g., a sterile formulation of a suitable soluble salt form of the antibody, can be dissolved and administered in a pharmaceutical excipient such as Water-for-Injection, 0.9% saline, or 5% glucose solution.[000318] In some embodiments, an antibody e.g., an anti-TCRpV9 antibody) is administered subcutaneously.[000319] In one embodiment, an antibody is administered via site- specific or targeted local delivery techniques. Examples of site- specific or targeted local delivery techniques include various implantable depot sources of the antibody or local delivery catheters, such as infusion catheters, an indwelling catheter, or a needle catheter, synthetic grafts, adventitial wraps, shunts and stents or other implantable devices, site specific carriers, direct injection, or direct application. See, e.g., International Publication No. WO 00 / 53211 and U.S. Patent No.5,981,568.[000320] In some embodiments, more than one antibody, or a combination of an antibody and another suitable therapeutic agent, may be administered to a subject in need of the treatment. The antibody can also be used in conjunction with other agents that serve to enhance and / or complement the effectiveness of the agents. Treatment efficacy for a target 7107489disease / disorder can be assessed by methods well-known in the art.[000321] The anti-TCRpV9 antibody and treatment methods involving such as described in the present disclosure may be utilized in combination with other types of therapy for the target disease or disorder disclosed herein. In this context, an antibody composition and a therapeutic agent may be given either simultaneously or sequentially. Examples include chemotherapy, immune therapy, surgery, radiation, gene therapy, and so forth, or antiinfection therapy. Such therapies can be administered simultaneously or sequentially (in any order) with the treatment according to the present disclosure.[000322] For example, the combination therapy can include the anti-TCRpV9 antibody and pharmaceutical composition described herein, co-formulated with and / or co-administered with, at least one additional therapeutic agent. Such combination therapies may advantageously utilize lower dosages of the administered therapeutic agents, thus preventing possible toxicities or complications associated with the various monotherapies.[000323] In some embodiments, a subject is administered a TCRPV9 antibodies and in combination with an additional therapeutic molecule. In some embodiments, the additional therapeutic molecule is an immunosuppressive.[000324] In some embodiments, anti-TCRpV9 antibodies provided herein are administered in combination with a T cell depleting agent. In some embodiments, a T cell depleting agent is an antibody to a surface antigen expressed by a T cell.[000325] Any of the anti-TCRpV9 antibodies and / or TCRPV9 targeting molecules disclosed herein can also be used for detecting presence of TCRPV9 in vitro or in vivo. Results obtained from such detection methods can be used for diagnostic purposes (e.g., diagnosing diseases associated with TCRPV9) or for scientific research purposes (e.g., identifying new TCRPV9 secreting cell types, studying bioactivity and / or regulation of secreted TCRPV9). For assay uses such as diagnostic uses, an anti-TCRpV9 antibody as described herein may be conjugated with a detectable label (e.g., an imaging agent such as a contrast agent) for detecting presence of TCRPV9 (e.g., soluble TCRPV9), either in vivo or in vitro.“Conjugated” or “attached” means two entities are associated, preferably with sufficient affinity that the therapeutic / diagnostic benefit of the association between the two entities is realized. The association between the two entities can be either direct or via a linker, such as a polymer linker. Conjugated or attached can include covalent or noncovalent bonding as well as other forms of association, such as entrapment, e.g., of one entity on or within the other, or of either or both entities on or within a third entity, such as a micelle.[000326] In other embodiments, an anti-TCRpV9 antibody as described herein can be 7107489attached to a detectable label, which is a compound that is capable of releasing a detectable signal, either directly or indirectly, such that the aptamer can be detected, measured, and / or qualified, in vitro or in vivo. Examples of such “detectable labels" are intended to include, but are not limited to, fluorescent labels, chemiluminescent labels, colorimetric labels, enzymatic markers, radioactive isotopes, and affinity tags such as biotin. Such labels can be conjugated to the aptamer, directly or indirectly, by conventional methods.[000327] In some embodiments, the detectable label is an agent suitable for detecting TCRPV9 expressing cells in vitro, which can be a radioactive molecule, a radiopharmaceutical, or an iron oxide particle. Radioactive molecules suitable for in vivo imaging include, but are not limited to,1221,1231,1241,1251,131I,18F,75Br,76Br,77Br,211At,225Ac,177LU,153Sm,186Re,188Re,67Cu,213Bi,212Bi,212Pb, and67Ga. Exemplary radiopharmaceuticals suitable for in vivo imaging includeinIn Oxyquinoline,131I Sodium iodide, "mTc Mebrofenin, and "mTc Red Blood Cells,123I Sodium iodide, "mTc Exametazime, "mTc Macroaggregate Albumin, "mTc Medronate, "mTc Mertiatide, "mTc Oxidronate, "mTc Pentetate, "mTc Pertechnetate, "mTc Sestamibi, "mTc Sulfur Colloid, "mTc Tetrofosmin, Thallium-201, or Xenon-133.[000328] The reporting agent can also be a dye, e.g., a fluorophore, which is useful in detecting a disease mediated by TCRPV9 expressing cells in tissue samples.[000329] To perform a diagnostic assay in vitro, an anti-TCRpV9 antibody can be brought in contact with a sample suspected of containing TCRPV9, e.g., TCRPV9 expressing cells or soluble TCRPV9 in disease microenvironment. The antibody and the sample may be incubated under suitable conditions for a suitable period to allow for binding of the antibody to the TCRPV9 antigen. Such an interaction can then be detected via routine methods, e.g., ELISA, histological staining or FACS. To perform a diagnostic assay in vivo, a suitable amount of anti-TCRpV9 antibodies, conjugated with a label (e.g., an imaging agent or a contrast agent), can be administered to a subject in need of the examination. Presence of the labeled antibody can be detected based on the signal released from the label by routine methods.[000330] To perform scientific research assays, an anti-TCRpV9 antibody can be used to study bioactivity of TCRPV9, detect the presence of TCRPV9 intracellularly, and or regulating the effect of TCRPV9. For example, a suitable amount of anti-TCRpV9 can be brought in contact with a sample (e.g. a new cell type that is not previously identified as TCRPV9 producing cells) suspected of producing TCRPV9. The cells are permeabilized prior to contacting the anti-TCRpV9 antibody. The antibody and the sample may be incubated 7107489under suitable conditions for a suitable period to allow for binding of the antibody to the TCRPV9 antigen. Such an interaction can then be detected via routine methods, e.g., ELISA, histological staining or FACS.VII. Kits for Therapeutic and Diagnostic Applications[000331] The present disclosure also provides kits for the therapeutic or diagnostic applications as disclosed herein. Such kits can include one or more containers comprising an anti-TCRpV9 antibody, e.g., any of those described herein.[000332] In some embodiments, the kit can comprise instructions for use in accordance with any of the methods described herein. The included instructions can comprise a description of administration of the anti-TCRpV9 antibody to treat, delay the onset, or alleviate a target disease as those described herein. The kit may further comprise a description of selecting an individual suitable for treatment based on identifying whether that individual has the target disease. In still other embodiments, the instructions comprise a description of administering an antibody to an individual at risk of the target disease.[000333] The instructions relating to the use of an anti-TCRpV9 antibody generally include information as to dosage, dosing schedule, and route of administration for the intended treatment. The containers may be unit doses, bulk packages (e.g., multi-dose packages) or sub-unit doses. Instructions supplied in the kits of the invention are typically written instructions on a label or package insert (e.g., a paper sheet included in the kit), but machine-readable instructions (e.g., instructions carried on a magnetic or optical storage disk) are also acceptable.[000334] The label or package insert indicates that the composition is used for treating, delaying the onset and / or alleviating a disease or disorder. Instructions may be provided for practicing any of the methods described herein.[000335] The kits of this invention are in suitable packaging. Suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging (e.g., sealed Mylar or plastic bags), and the like.[000336] Also contemplated are packages for use in combination with a specific device, such as an infusion device, such as a minipump. A kit may have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). The container may also have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). At least one active agent in the composition is an anti-TCRpV9 7107489antibody as those described herein.[000337] Kits may optionally provide additional components such as buffers and interpretive information. Normally, the kit comprises a container and a label or package insert(s) on or associated with the container. In some embodiments, the invention provides articles of manufacture comprising contents of the kits described above.[000338] Also provided herein are kits for use in detecting TCRPV9 and / or TCRpV9-positive cells (e.g., T cells) in a sample (e.g., blood or other tissue). Such a kit may comprise any of the anti-TCRpV9 antibodies described herein. In some instances, the anti-TCRpV9 antibody can be conjugated with a detectable label as those described herein. Detection of TCRPV9-expressing cells can be useful in diagnosing an autoimmune condition.[000339] Alternatively or in addition, the kit may comprise a secondary antibody capable of binding to anti-TCRpV9 antibody. The kit may further comprise instructions for using the anti-TCRpV9 antibody for detecting TCRPV9.EXAMPLESExample 1: Anti-TCR|JV9 Variable Heavy Chain and Variable Light Chain Pairs Binding Affinity[000340] Deep mutational scanning on a humanized anti-TCRpV9 antibody and new humanization CDR grafting of rat variable heavy (VH) and variable light (VL) sequences was performed to produce anti-TCRpV9 antibody variants (VH and VL sequences shown in Table 11 and Table 15, respectively). Antibody variants were expressed in Chinese Hamster Ovary (CHO) cells. Expression metrics are shown in Table El.[000341] Multi-point kinetics (affinity) to recombinant TCRPV9 protein having an acidic helix zipper (“Analyte”; SEQ ID NO: 1036, shown below) was tested at high-throughput and small scale using Carterra LSA. CHO supernatants were batch diluted and captured by antihuman Fc lawn on Carterra LSA. Kinetics of antibody variant binding to recombinant TCRPV9 was measured by five-point non-regenerative kinetics with five minute association and 10 minute disassociation phases. Binding and expression metrics are shown in Table EL [000342] A Comparator Pair having a VH of SEQ ID NO: 1 and a VL of SEQ ID NO: 2 (CDR and framework numbering shown in FIGs. 1-2) was used as a control. Several anti-TCRPV9 VH and VL pairs exhibited increased affinity for TCR[3V9 relative to the Comparator Pair, including Pairs 51 (kD = 8.21 x 1011), 376 (kD = 4.02 x IO10), and 378-395 (kD = 1.02 x IO’10, 1.08 x IO’10, 1.5 x IO’10, 2.19 x IO’10, 2.24 x IO’10, 2.46 x IO’10, 2.84 x IO’10, 2.89 x IO’10, 3.63 x IO’10, 4.05 x IO’10, 4.2 x IO’10, 4.41 x IO’10, 4.64 x IO’10, 4.86 x IO’10, 71074895 x IO10, and 5 x IO10, respectively).Analyte sequence:GVTQTPKHLITATGQRVTLRCSPRSGDLSVYWYQQSLDQGLQ FLIQYYNGEERAKGNILERFSAQQFPDLHSELNLSSLELGDS ALYFCASSVGLFSTDTQYFGPGTRLTVLEDLKNVFPPEVAVF EPSEAEISHTQKATLVCLATGFYPDHVELS WWVNGKE VH S GV CTDPQPLKEQPALNDSRYALSSRLRVSATFWQNPRNHFRCQV QFYGLSENDEWTQDRAKPVTQIVSAEAWGRADAQLEKELQAL EKENAQLEWELQALEKELAQ ( SEQ ID NO : 1036; acidichelix zipper in bold)Table El. Variable Heavy Chain and Variable Light Chain Pair Binding Affinity71074897107489710748971074897107489710748971074897107489710748971074897107489710748971074897107489710748971074897107489710748971074897107489710748971074897107489*N / A indicates that binding was below the lower limit of detection.Example 2: Further Testing of Select Anti-TCR V9 Variable Heavy Chain and Variable Light Chain PairsProtein binding affinity by SPR[000343] Binding affinities of antibodies to recombinant human TRBV9+ TCR protein were7107489determined on Carterra SPR instrument. Antibodies were immobilized on chips and recombinant TRBV9-TCR were serially diluted and binding with captured antibodies was measured at RT and pH 7.4. Kinetic binding parameters KD, Kd and Ka were determined.Selectivity with TCRs by Octet[000344] TRBV7-9 was selected for antibody selectivity study because TRBV7-9’s sequence is the most similar to TRBV9 among all TRBV families. The antibodies were captured to Octet sensor and then their binding to recombinant TRBV7-9 TCR protein was assessed at RT and pH 7.0. Binding was evaluated with positive controls (TRBV9).Cell binding affinity[000345] Binding affinities of antibodies to primary human TRBV9+ T cells, isolated from peripheral blood mononuclear cells (PBMCs), were determined using serially diluted antibodies incubated with the cells for 1 hour at 4°C. Next cells were washed then binding of antibodies were detected with fluorophore conjugated anti-human secondary antibody. Flow cytometric analysis was performed to measure the mean fluorescence intensity (MFI) and EC50 values were subsequently calculated.In vitro cell killing activity[000346] In vitro functional activity of antibodies was evaluated in primary human TRBV9+ T cells isolated from PBMCs. Serially diluted antibodies were incubated with target cells and effector cells or human serum at 37 °C and pH 7.2 for 16 hrs. Detection of cell killing was measured by luminescence of reporter gene expression in effector cells or loss of target cell number. The EC50 values were subsequently calculated.Humanness[000347] Humanness was calculated based on the number of amino acid differences in the V region compared with the germline sequences (IGHV7-4-l*02 / IGHJ4*01 and IGKV1-16*01 / IGKJ2*01) used for humanization.[000348] Results are shown in Table E2.[000349] Table E2. Variable Heavy Chain and Variable Light Chain Pair Characteristics7107489<<[000350] Table E2 continued. Variable Heavy Chain and Variable Light Chain Pair Characteristics<<NB = no bindingOTHER EMBODIMENTS[000351] All of the features disclosed in this specification may be combined in any combination. Each feature disclosed in this specification may be replaced by an alternative feature serving the same, equivalent, or similar purpose. Thus, unless expressly stated otherwise, each feature disclosed is only an example of a generic series of equivalent or similar features.7107489[000352] From the above description, one skilled in the art can easily ascertain the essential characteristics of the present invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions. Thus, other embodiments are also set forth as follows:EQUIVALENTS AND SCOPE[000353] In the claims, articles such as “a,” “an,” and “the” may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include “or” between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The invention includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The invention includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process.[000354] Furthermore, the invention encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, and descriptive terms from one or more of the listed claims is introduced into another claim. For example, any claim that is dependent on another claim can be modified to include one or more limitations found in any other claim that is dependent on the same base claim. Where elements are presented as lists, e.g., in Markush group format, each subgroup of the elements is also disclosed, and any element(s) can be removed from the group. It should it be understood that, in general, where the invention, or aspects of the invention, is / are referred to as comprising particular elements and / or features, certain embodiments of the invention or aspects of the invention consist, or consist essentially of, such elements and / or features. For purposes of simplicity, those embodiments have not been specifically set forth in haec verba herein.[000355] The phrase “and / or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with “and / or” should be construed in the same fashion, i.e., “one or more” of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to “A and / or B”, when7107489used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.[000356] As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of’ or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives i.e. “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.” “Consisting essentially of,” when used in the claims, shall have its ordinary meaning as used in the field of patent law.[000357] As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and / or B”) can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc.[000358] It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or act, the order of the steps or acts7107489of the method is not necessarily limited to the order in which the steps or acts of the method are recited.[000359] In the claims, as well as in the specification above, all transitional phrases such as “comprising,” “including,” “carrying,” “having,” “containing,” “involving,” “holding,” “composed of,” and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases “consisting of’ and “consisting essentially of’ shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03. It should be appreciated that embodiments described in this document using an open-ended transitional phrase (e.g., “comprising”) are also contemplated, in alternative embodiments, as “consisting of’ and “consisting essentially of’ the feature described by the open-ended transitional phrase. For example, if the application describes “a composition comprising A and B,” the application also contemplates the alternative embodiments “a composition consisting of A and B” and “a composition consisting essentially of A and B.”[000360] Where ranges are given, endpoints are included. Furthermore, unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or sub-range within the stated ranges in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise.[000361] This application refers to various issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. If there is a conflict between any of the incorporated references and the instant specification, the specification shall control. In addition, any particular embodiment of the present invention that falls within the prior art may be explicitly excluded from any one or more of the claims. Because such embodiments are deemed to be known to one of ordinary skill in the art, they may be excluded even if the exclusion is not set forth explicitly herein. Any particular embodiment of the invention can be excluded from any claim, for any reason, whether or not related to the existence of prior art.[000362] Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific embodiments described herein. The scope of the present embodiments described herein is not intended to be limited to the above Description, but rather is as set forth in the appended claims. Those of ordinary skill in the art will appreciate that various changes and modifications to this description may be made7107489without departing from the spirit or scope of the present invention, as defined in the following claims.[000363] The recitation of a listing of chemical groups in any definition of a variable herein includes definitions of that variable as any single group or combination of listed groups. The recitation of an embodiment for a variable herein includes that embodiment as any single embodiment or in combination with any other embodiments or portions thereof. The recitation of an embodiment herein includes that embodiment as any single embodiment or in combination with any other embodiments or portions thereof.7107489

Claims

CLAIMSWhat is claimed is:

1. A polypeptide comprising an amino acid sequence having at least 70% identity with the amino acid sequence of SEQ ID NO: 1, wherein the amino acid sequence has one or more alterations relative to the amino acid sequence of SEQ ID NO: 1.

2. The polypeptide of claim 1, wherein the amino acid sequence comprises, relative to the amino acid sequence of SEQ ID NO: 1, one or more of the alterations provided in Table 1.

3. The polypeptide of claim 1 or claim 2, wherein the polypeptide comprises a consensus sequence of SEQ ID NO: 1034 (X!-X125), wherein each X is as provided for in Table 2.

4. A polypeptide comprising an amino acid sequence having at least 80% identity with an amino acid sequence provided in Table 3.

5. The polypeptide of any one of claims 1-4, wherein the polypeptide is less immunogenic in humans relative to a polypeptide consisting of the amino acid sequence of SEQ ID NO: 1.

6. A polypeptide comprising an amino acid sequence having at least 70% identity with the amino acid sequence of SEQ ID NO: 2, wherein the amino acid sequence has one or more alterations relative to the amino acid sequence of SEQ ID NO: 2.

7. The polypeptide of claim 6, wherein the amino acid sequence comprises, relative to the amino acid sequence of SEQ ID NO: 2, one or more of the alterations provided in Table 4.

8. The polypeptide of claim 6 or claim 7, wherein the polypeptide comprises a consensus sequence of SEQ ID NO: 1035 (X^X107), wherein each X is as provided for in Table 5.

9. A polypeptide comprising an amino acid sequence having at least 80% identity with an amino acid sequence provided in Table 6.710748910. The polypeptide of any one of claims 6-9, wherein the polypeptide is less immunogenic in humans relative to a polypeptide consisting of the amino acid sequence of SEQ ID NO: 2.

11. A polynucleotide comprising a nucleotide sequence encoding the polypeptide of any one of claims 1-10.

12. An expression vector comprising a nucleotide sequence encoding the polypeptide of any one of claims 1-10.

13. A cell comprising the polypeptide of any one of claims 1-10, the polynucleotide of claim 11, or the expression vector of claim 12.

14. A cell comprising one or more polynucleotides collectively comprising a first nucleotide sequence encoding a first polypeptide and a second nucleotide sequence encoding a second polypeptide, wherein the first polypeptide is according to any one of claims 1-5, and wherein the second polypeptide is according to any one of claims 6-10.

15. The cell of claim 14, wherein the cell expresses a first polypeptide, second polypeptide pair provided in Table 7.

16. A method of producing a polypeptide, the method comprising:(i) culturing the cell of any one of claims 13-15 under conditions suitable for expression of the polypeptide(s) by the cell;(ii) harvesting the polypeptide(s); and(iii) optionally purifying the polypeptide(s).

17. A TCRPV9 targeting molecule comprising an antibody that specifically binds to TCRPV9, wherein the antibody comprises a heavy chain variable domain comprising:a CDR1 having the amino acid sequence of a CDR1 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with a CDR1 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3;7107489a CDR2 having the amino acid sequence of a CDR2 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with a CDR2 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3; anda CDR3 having the amino acid sequence of a CDR3 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with a CDR3 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3.

18. The TCRPV9 targeting molecule of claim 17, wherein the CDRs of the heavy chain variable domain are determined according to Kabat.

19. The TCRPV9 targeting molecule of claim 17, wherein the CDRs of the heavy chain variable domain are determined according to Chothia.

20. The TCRPV9 targeting molecule of claim 17, wherein the CDRs of the heavy chain variable domain are determined according to IMGT.

21. The TCRPV9 targeting molecule of claim 17, wherein the CDRs of the heavy chain variable domain are determined according to AbM.

22. The TCRPV9 targeting molecule of claim 17, wherein the CDRs of the heavy chain variable domain are determined according to Contact.

23. A TCRPV9 targeting molecule comprising an antibody that specifically binds to TCRPV9, wherein the antibody comprises a heavy chain variable domain comprising:a CDR1 having the amino acid sequence of DYLVH (SEQ ID NO: 3) or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 3;a CDR2 having the amino acid sequence of WINTYTGTPTYADDFEG (SEQ ID NO: 4) or an amino acid sequence having 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 4; and7107489a CDR3 having the amino acid sequence of SWRRGLRGIGFDY (SEQ ID NO: 5) or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 5,wherein the CDRs are determined according to Kabat; andwherein the amino acid sequence of the heavy chain variable domain comprises one or more alterations relative to the amino acid sequence of SEQ ID NO: 1.

24. The TCRPV9 targeting molecule of any one of claims 17-23, wherein the heavy chain variable domain has increased affinity to TCRPV9 relative to a heavy chain variable domain consisting of the amino acid sequence of SEQ ID NO: 1.

25. The TCRPV9 targeting molecule of any one of claims 17-24, wherein the heavy chain variable domain is less immunogenic in humans relative to a heavy chain variable domain consisting of the amino acid sequence of SEQ ID NO: 1.

26. The TCRPV9 targeting molecule of any one of claims 17-25, wherein the heavy chain variable domain does not comprise a CDR1, CDR2, and CDR3 of SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, respectively, wherein the CDRs are determined according to Kabat.

27. The TCRPV9 targeting molecule of any one of claims 17-26, wherein the heavy chain variable domain comprises:a CDR1 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 3, one or more of the CDR1 alterations provided in Table 8;a CDR2 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 4, one or more of the CDR2 alterations provided in Table 8; and / or a CDR3 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 5, one or more of the CDR3 alterations provided in Table 8;wherein the CDRs are determined according to Kabat.

28. The TCRPV9 targeting molecule of any one of claims 17-27, wherein the heavy chain variable domain comprises:a CDR1 comprising an amino acid sequence provided for a CDR1 in Table 9;a CDR2 comprising an amino acid sequence provided for a CDR2 in Table 9; and / or 7107489a CDR3 comprising an amino acid sequence provided for a CDR3 in Table 9; wherein the CDRs are determined according to Kabat.

29. The TCRPV9 targeting molecule of any one of claims 17-28, wherein the heavy chain variable domain comprises a CDR1, CDR2, and CDR3 combination provided in Table 9, wherein the CDRs are determined according to Kabat.

30. The TCRPV9 targeting molecule of any one of claims 17-29, wherein the heavy chain variable domain comprises:a FR1 having the amino acid sequence of a FR1 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR1 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3;a FR2 having the amino acid sequence of a FR2 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR2 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3;a FR3 having the amino acid sequence of a FR3 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR3 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3; and / ora FR4 having the amino acid sequence of a FR4 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR4 of a heavy chain variable domain comprising an amino acid sequence provided in Table 3.

31. The TCRPV9 targeting molecule of claim 30, wherein the FRs of the heavy chain variable domain are determined according to Kabat.

32. The TCRPV9 targeting molecule of claim 30, wherein the FRs of the heavy chain variable domain are determined according to Chothia.

33. The TCRPV9 targeting molecule of claim 30, wherein the FRs of the heavy chain variable domain are determined according to IMGT.710748934. The TCRPV9 targeting molecule of claim 30, wherein the FRs of the heavy chain variable domain are determined according to AbM.

35. The TCRPV9 targeting molecule of claim 30, wherein the FRs of the heavy chain variable domain are determined according to Contact.

36. The TCRPV9 targeting molecule of any one of claims 17-35, wherein the heavy chain variable domain comprises:a FR1 having the amino acid sequence of QVQLVQSGSELKKPGESVKVSCKASGYTFT (SEQ ID NO: 6) or an amino acid sequence having 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 6;a FR2 having the amino acid sequence of WVRQAPGQGLEWMG (SEQ ID NO: 7) or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 7;a FR3 having the amino acid sequence of RFVFSLDTSVSTANLQISSLKAEDTAVYFCAR (SEQ ID NO: 8) or an amino acid sequence having 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 8; and / ora FR4 having the amino acid sequence of WGQGTLVTVSS (SEQ ID NO: 9) or an amino acid sequence having 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 5;wherein the FRs are determined according to Kabat.

37. The TCRPV9 targeting molecule of any one of claims 17-36, wherein the heavy chain variable domain does not comprise a FR1, FR2, FR3, and FR4 of SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9, respectively, wherein the FRs are determined according to Kabat.

38. The TCRPV9 targeting molecule of any one of claims 17-37, wherein the heavy chain variable domain comprises:a FR1 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 6, one or more of the FR1 alterations provided in Table 10;7107489a FR2 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 7, one or more of the FR2 alterations provided in Table 10;a FR3 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 8, one or more of the FR3 alterations provided in Table 10; and / ora FR4 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 9, one or more of the FR4 alterations provided in Table 10;wherein the FRs are determined according to Kabat.

39. The TCRPV9 targeting molecule of any one of claims 17-38, wherein the heavy chain variable domain comprises:a FR1 comprising an amino acid sequence provided for a FR1 in Table 11;a FR2 comprising an amino acid sequence provided for a FR2 in Table 11;a FR3 comprising an amino acid sequence provided for a FR3 in Table 11; and / or a FR4 comprising an amino acid sequence provided for a FR4 in Table 11; wherein the FRs are determined according to Kabat.

40. The TCRPV9 targeting molecule of any one of claims 17-39, wherein the heavy chain variable domain comprises a FR1, FR2, FR3, and FR4 combination provided in Table 11, wherein the FRs are determined according to Kabat.

41. The TCRPV9 targeting molecule of any one of claims 17-40, wherein the heavy chain variable domain comprises an amino acid sequence having at least 80% identity with an amino acid sequence provided in Table 3.

42. The TCRPV9 targeting molecule of any one of claims 17-41, wherein the heavy chain variable domain consists of an amino acid sequence an amino acid sequence provided in Table 3.

43. The TCRPV9 targeting molecule of any one of claims 17-42 further comprising a light chain variable domain, wherein the light chain variable domain comprises:a CDR1 having the amino acid sequence of a CDR1 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with a CDR1 of a light chain variable domain comprising an amino acid sequence provided in Table 6;7107489a CDR2 having the amino acid sequence of a CDR2 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with a CDR2 of a light chain variable domain comprising an amino acid sequence provided in Table 6; anda CDR3 having the amino acid sequence of a CDR3 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with a CDR3 of a light chain variable domain comprising an amino acid sequence provided in Table 6.

44. The TCRPV9 targeting molecule of claim 43, wherein the CDRs of the light chain variable domain are determined according to Kabat.

45. The TCRPV9 targeting molecule of claim 43, wherein the CDRs of the light chain variable domain are determined according to Chothia.

46. The TCRPV9 targeting molecule of claim 43, wherein the CDRs of the light chain variable domain are determined according to IMGT.

47. The TCRPV9 targeting molecule of claim 43, wherein the CDRs of the light chain variable domain are determined according to AbM.

48. The TCRPV9 targeting molecule of claim 43, wherein the CDRs of the light chain variable domain are determined according to Contact.

49. The TCRPV9 targeting molecule of any one of claims 17-48, wherein the antibody that specifically binds to TCRPV9 further comprises a light chain variable domain, wherein the light chain variable domain comprises:a CDR1 having the amino acid sequence of KASKSINKYL (SEQ ID NO: 10) or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 10;a CDR2 having the amino acid sequence of DGSTLQS (SEQ ID NO: 11) or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 11; and7107489a CDR3 having the amino acid sequence of QQHNEYPPT (SEQ ID NO: 12) or an amino acid sequence having 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 12,wherein the CDRs are determined according to Kabat.

50. The TCRPV9 targeting molecule of any one of claims 43-49, wherein the amino acid sequence of the light chain variable domain comprises one or more alterations relative to the amino acid sequence of SEQ ID NO: 2.

51. The TCRPV9 targeting molecule of any one of claims 43-50, wherein the light chain variable domain has increased affinity to TCRPV9 relative to a light chain variable domain consisting of the amino acid sequence of SEQ ID NO: 2.

52. The TCRPV9 targeting molecule of any one of claims 43-51, wherein the light chain variable domain is less immunogenic in humans relative to a heavy chain variable domain consisting of the amino acid sequence of SEQ ID NO: 2.

53. The TCRPV9 targeting molecule of any one of claims 43-52, wherein the light chain variable domain does not comprise a CDR1, CDR2, and CDR3 of SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12, respectively, wherein the CDRs are determined according to Kabat.

54. The TCRPV9 targeting molecule of any one of claims 43-53, wherein the light chain variable domain comprises:a CDR1 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 10, one or more of the CDR1 alterations provided in Table 12; a CDR2 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 11, one or more of the CDR2 alterations provided in Table 12; and / ora CDR3 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 12, one or more of the CDR3 alterations provided in Table 12; wherein the CDRs are determined according to Kabat.710748955. The TCRPV9 targeting molecule of any one of claims 43-54, wherein the light chain variable domain comprises:a CDR1 comprising an amino acid sequence provided for a CDR1 in Table 13; a CDR2 comprising an amino acid sequence provided for a CDR2 in Table 13; and / or a CDR3 comprising an amino acid sequence provided for a CDR3 in Table 13; wherein the CDRs are determined according to Kabat.

56. The TCRPV9 targeting molecule of any one of claims 43-55, wherein the light chain variable domain comprises a CDR1, CDR2, and CDR3 combination provided in Table 13, wherein the CDRs are determined according to Kabat.

57. The TCRPV9 targeting molecule of any one of claims 43-56, wherein the light chain variable domain comprises:a FR1 having the amino acid sequence of a FR1 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR1 of a light chain variable domain comprising an amino acid sequence provided in Table 6;a FR2 having the amino acid sequence of a FR2 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR2 of a light chain variable domain comprising an amino acid sequence provided in Table 6;a FR3 having the amino acid sequence of a FR3 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR3 of a light chain variable comprising an amino acid sequence domain provided in Table 6; and / ora FR4 having the amino acid sequence of a FR4 of a light chain variable domain comprising an amino acid sequence provided in Table 6 or an amino acid sequence having 5, 4, 3, 2, or 1 amino acid alteration(s) with a FR4 of a light chain variable domain comprising an amino acid sequence provided in Table 6.

58. The TCRPV9 targeting molecule of claim 57, wherein the FRs of the light chain variable domain are determined according to Kabat.710748959. The TCRPV9 targeting molecule of claim 57, wherein the FRs of the light chain variable domain are determined according to Chothia.

60. The TCRPV9 targeting molecule of claim 57, wherein the FRs of the light chain variable domain are determined according to IMGT.

61. The TCRPV9 targeting molecule of claim 58, wherein the FRs of the light chain variable domain are determined according to AbM.

62. The TCRPV9 targeting molecule of claim 58, wherein the FRs of the light chain variable domain are determined according to Contact.

63. The TCRPV9 targeting molecule of any one of claims 43-62, wherein the light chain variable domain comprises:a FR1 having the amino acid sequence of DIQMTQSPYSLSASVGDRVTITC (SEQ ID NO: 13) or an amino acid sequence having 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 13;a FR2 having the amino acid sequence of AWFQQKPGKPNKLLIY (SEQ ID NO: 14) or an amino acid sequence having 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 14;a FR3 having the amino acid sequence of GVPSRFSGSGSGTDFTLTISSLEPEDFATYYC (SEQ ID NO: 15) or an amino acid sequence having 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 15; and / ora FR4 having the amino acid sequence of FGQGTKLEIK (SEQ ID NO: 16) or an amino acid sequence having 4, 3, 2, or 1 amino acid alteration(s) with the amino acid sequence of SEQ ID NO: 16;wherein the FRs are determined according to Kabat.

64. The TCRPV9 targeting molecule of any one of claims 43-63, wherein the light chain variable domain does not comprise a FR1, FR2, FR3, and FR4 of SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, and SEQ ID NO: 16, respectively, wherein the FRs are determined according to Kabat.710748965. The TCRPV9 targeting molecule of any one of claims 43-64, wherein the light chain variable domain comprises:a FR1 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 13, one or more of the FR1 alterations provided in Table 14;a FR2 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 14, one or more of the FR2 alterations provided in Table 14;a FR3 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 15, one or more of the FR3 alterations provided in Table 14; and / ora FR4 comprising an amino acid sequence having, relative to the amino acid sequence of SEQ ID NO: 16, one or more of the FR4 alterations provided in Table 14;wherein the FRs are determined according to Kabat.

66. The TCRPV9 targeting molecule of any one of claims 43-65, wherein the light chain variable domain comprises:a FR1 comprising an amino acid sequence provided for a FR1 in Table 15;a FR2 comprising an amino acid sequence provided for a FR2 in Table 15;a FR3 comprising an amino acid sequence provided for a FR3 in Table 15; and / or a FR4 comprising an amino acid sequence provided for a FR4 in Table 15; wherein the FRs are determined according to Kabat.

67. The TCRPV9 targeting molecule of any one of claims 43-66, wherein the light chain variable domain comprises a FR1, FR2, FR3, and FR4 combination provided in Table 15, wherein the FRs are determined according to Kabat.

68. The TCRPV9 targeting molecule of any one of claims 43-67, wherein the light chain variable domain comprises an amino acid sequence having at least 80% identity with an amino acid sequence provided in Table 6.

69. The TCRPV9 targeting molecule of any one of claims 43-68, wherein the light chain variable domain consists of an amino acid sequence an amino acid sequence provided in Table 6.710748970. The TCRPV9 targeting molecule of any one of claims 43-69, wherein the TCRPV9 targeting molecule comprises a heavy chain variable domain, light chain variable domain pair provided in Table 16.

71. A polynucleotide comprising or a combination of polynucleotides collectively comprising a nucleotide sequence encoding the TCRPV9 targeting molecule of any one of claims 17-70.

72. An expression vector comprising a nucleotide sequence encoding the TCRPV9 targeting molecule of any one of claims 17-70.

73. A cell comprising the TCRPV9 targeting molecule of any one of claims 17-70, the polynucleotide or combination of polynucleotides of claim 71, or the expression vector of claim 72.

74. A method of producing a TCRPV9 targeting molecule, the method comprising:(i) culturing the cell of claim 73 under conditions suitable for expression of the TCRPV9 targeting molecule by the cell;(ii) harvesting the TCRPV9 targeting molecule; and(iii) optionally purifying the TCRPV9 targeting molecule.

75. A composition comprising:the TCRPV9 targeting molecule of any one of claims 17-70, the polynucleotide or combination of polynucleotides of claim 71, the expression vector of claim 72, or the cell of claim 73; anda pharmaceutically acceptable excipient.

76. A method of treating or preventing a disease or condition characterized by expression of T cell receptor beta variable 9 (TCRPV9) in a subject, the method comprising administering to the subject the TCRPV9 targeting molecule of one of claims 17-70, the polynucleotide or the combination of polynucleotides of claim 71, the expression vector of claim 72, the cell of claim 73, or the composition of claim 75.710748977. The method of claim 76, wherein the disease or condition is any T cell-mediated autoimmune or autoinflammatory disease.

78. The method of claim 76, wherein the disease or condition characterized by expression of TCRPV9 is an autoimmune disease.

79. The method of claim 78, wherein the autoimmune disease is ankylosing spondylitis, celiac disease, inflammatory bowel disease, psoriatic arthritis, or multiple sclerosis.

80. The method of claim 78, wherein the autoimmune disease is ankylosing spondylitis.

81. A method of reducing the number of cells expressing T cell receptor beta variable 9 (TCRPV9) in a subject, the method comprising administering to the subject the TCRPV9 targeting molecule of one of claims 17-70, the polynucleotide or the combination of polynucleotides of claim 71, the expression vector of claim 72, the cell of claim 73, or the composition of claim 75.

82. The method of any one of claims 76-81, wherein the TCRPV9 targeting molecule increases killing of cells expressing TCRPV9 relative to killing of cells expressing TCRPV9 prior to the administration.

83. The method of any one of claims 76-81, wherein the TCRPV9 targeting molecule reduces the level of TCRPV9 in the blood of the subject.

84. A method for detecting T cell receptor beta variable 9 (TCRPV9) in a sample, the method comprising contacting a sample with the TCRPV9 targeting molecule of any one of claims 17-70 and detecting the formation of a complex of the TCRPV9 targeting molecule with TCRPV9.

85. A kit comprising one or more containers comprising the TCRPV9 targeting molecule of one of claims 17-70, the polynucleotide or the combination of polynucleotides of claim 71, the expression vector of claim 72, the cell of claim 73, or the composition of claim 75.7107489

Images