Compositions and methods for modulating beta chain mediated immunity

Abstract

Anti-Vβ17 antibodies or antigen-binding fragments thereof are described. Nucleic acids encoding the antibodies, compositions comprising the antibodies, methods of making the antibodies, and methods of using the antibodies to treat or prevent disease are also described.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Provisional Patent Application No. 63 / 274,430, filed November 1, 2021, U.S. Provisional Patent Application No. 63 / 274,446, filed November 1, 2021, and U.S. Provisional Patent Application No. 63 / 274,449, filed November 1, 2021, the disclosures of which are incorporated by reference in their entireties herein.

[0002] (Reference to electronically submitted sequence listing) This application contains a sequence listing that has been submitted electronically. The contents of the electronic sequence listing (065768-135WO1_Sequence Listing.xml; size: 512333 bytes; and creation date: October 31, 2022) are incorporated herein by reference in their entirety.

[0003] (Field) In certain aspects, provided herein are antibodies that bind to Vβ17, as well as recombinant cells containing vectors and compositions that include the antibodies. Methods of making and using the antibodies are also provided.

[0004] (overview) In one aspect, the disclosure provides an antibody that binds Vβ17, comprising a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 31, wherein the VH comprises VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively; and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 32, wherein the VL comprises VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively.

[0005] In another aspect, the disclosure provides an antibody that binds Vβ17, comprising a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of the VH having the amino acid sequence of SEQ ID NO: 65, and a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of the VL having the amino acid sequence of SEQ ID NO: 66.

[0006] In one embodiment, the disclosure provides an antibody that binds to Vβ17, comprising a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 99, and a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 100.

[0007] In another embodiment, the disclosure provides an antibody that binds to Vβ17, comprising a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of the VH having the amino acid sequence of SEQ ID NO: 133, and a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of the VL having the amino acid sequence of SEQ ID NO: 134.

[0008] In one aspect, the disclosure provides an antibody that binds to Vβ17, comprising a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 167; and a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 168.

[0009] In another aspect, the disclosure provides an antibody that binds to Vβ17, comprising a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 201; and a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 202.

[0010] In one embodiment, the disclosure provides an antibody that binds to Vβ17, comprising a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 235; and a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 236.

[0011] In another embodiment, the disclosure provides an antibody that binds to Vβ17, comprising a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 269; and a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 270.

[0012] In one aspect, the disclosure provides an antibody that binds to Vβ17, comprising a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 303; and a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 304.

[0013] In another aspect, the disclosure provides an antibody that binds to Vβ17, comprising a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 337; and a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 338.

[0014] In one embodiment, the disclosure provides an antibody that binds to Vβ17, comprising a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 371; and a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 372.

[0015] In another embodiment, the disclosure provides an antibody that binds to Vβ17, comprising a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 405; and a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 406.

[0016] In one aspect, the disclosure provides an antibody that binds Vβ17, comprising a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 439; and a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 440.

[0017] The disclosure also provides antibodies, wherein the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 are according to the Kabat numbering system.

[0018] The disclosure also provides antibodies, wherein the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 are according to the Chothia numbering system.

[0019] The disclosure also provides antibodies, wherein the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 are according to the AbM numbering system.

[0020] The disclosure also provides antibodies, wherein the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 are according to the Contact numbering system.

[0021] The disclosure also provides antibodies, wherein the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 are according to the IMGT numbering system.

[0022] The disclosure also provides an antibody, wherein the antibody is a humanized antibody.

[0023] The disclosure also provides an antibody, wherein the antibody is an IgG antibody. The disclosure also provides an antibody, wherein the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

[0024] The disclosure also provides an antibody, wherein the antibody comprises a kappa light chain.The disclosure also provides an antibody, wherein the antibody comprises a lambda light chain.

[0025] The disclosure also provides an antibody, wherein the antibody is a monoclonal antibody.

[0026] The disclosure also provides antibodies, where the antibodies bind to the Vβ17 antigen.The disclosure also provides antibodies, where the antibodies bind to the Vβ17 epitope.

[0027] The disclosure also provides an antibody, wherein the antibody specifically binds to Vβ17.

[0028] The present disclosure also provides an antibody, wherein the antibody is multivalent. The present disclosure also provides an antibody, wherein the antibody is capable of binding to at least three antigens. The present disclosure also provides an antibody, wherein the antibody is capable of binding to at least four antigens. The present disclosure also provides an antibody, wherein the antibody is capable of binding to at least five antigens.

[0029] The present disclosure also provides for antibodies, where the antibody is a multispecific antibody. The present disclosure also provides for antibodies, where the antibody is a bispecific antibody. The present disclosure also provides for antibodies, where the antibody is a trispecific antibody. The present disclosure also provides for antibodies, where the antibody is a tetraspecific antibody.

[0030] In one aspect, the disclosure provides a nucleic acid encoding an antibody described herein.

[0031] In one aspect, the disclosure provides a vector comprising a nucleic acid disclosed herein.

[0032] In one aspect, the disclosure provides a host cell comprising the vector disclosed herein.

[0033] In one aspect, the disclosure provides a kit comprising a vector disclosed herein and instructions for using the vector.In one aspect, the disclosure provides a kit comprising an antibody disclosed herein and instructions for using the antibody.

[0034] In one aspect, the disclosure provides a pharmaceutical composition comprising an antibody disclosed herein and a pharma- ceutically acceptable carrier.

[0035] In one aspect, the disclosure provides a method of producing a pharmaceutical composition disclosed herein, comprising combining an antibody with a pharma- ceutically acceptable carrier to obtain a pharmaceutical composition.

[0036] In one aspect, the disclosure provides a method of activating a T cell that expresses Vβ17, the method comprising contacting a T cell that expresses Vβ17 with an antibody disclosed herein.

[0037] The present disclosure also provides methods in which contacting increases expression of CD69, CD25, and / or granzyme B compared to T cells expressing Vβ17 that have not been contacted with an antibody disclosed herein.

[0038] In one aspect, the disclosure provides a process for making an antibody that binds to two or more target molecules, the process comprising steps for performing the functions of obtaining a first binding domain that binds to Vβ17 present on a T cell, obtaining a second binding domain that binds to a second target on the surface of the target cell, and providing an antibody that binds to Vβ17 present on a T cell and the second target on the surface of the target cell.

[0039] The disclosure also provides a process comprising repeating the steps n times to serve to obtain a second binding domain that binds to a second target on the surface of a target cell, further comprising n steps to serve to provide a first binding domain that binds to Vβ17 present on a T cell and n target molecules, where n is at least 2.

[0040] In one aspect, the disclosure provides a process for making an antibody disclosed herein, the process comprising growing a host cell disclosed herein under conditions to produce the antibody, hi another aspect, the method further comprises isolating the antibody.

[0041] In one aspect, a method is provided for directing a T cell expressing Vβ17 to a target cell, comprising contacting an antibody disclosed herein with the target cell, wherein a second target is present on the surface of the target cell, and the contacting directs the T cell to the target cell.

[0042] In one aspect, a method of inhibiting growth or proliferation of a target cell is provided, comprising contacting an antibody disclosed herein with a target cell having a second target present on the surface of the target cell, wherein the contacting is in the presence of a T cell expressing Vβ17, and wherein the contacting results in inhibition of growth or proliferation of the target cell.

[0043] In one aspect, a method of eliminating a target cell in a subject is provided, comprising contacting an antibody disclosed herein with a target cell having a second target present on the surface of the target cell, wherein the contacting is in the presence of a T cell expressing Vβ17, and wherein the contacting results in elimination of the target cell.

[0044] In one aspect, a method of treating a disease in a subject is provided, comprising administering to the subject an effective amount of an antibody disclosed herein, wherein the disease is caused in whole or in part by a target cell having a second target present on the surface of the target cell. In another embodiment, the subject is a human. In one embodiment, the subject is a subject in need thereof. [Brief description of the drawings]

[0045] The foregoing Summary of the Invention, as well as the following Detailed Description of certain embodiments of the present application, will be better understood when read in conjunction with the accompanying drawings. It should be understood, however, that the present application is not limited to the precise embodiments shown in the drawings. [Figure 1] Several monoclones with specific binding to Vβ17, identified by flow cytometry using different cell lines and primary cells, are shown. [Diagram 2] Figure 2 shows that 26 monoclones induce proliferation of Vβ17+ cells. [Diagram 3] Figure 1 shows the different growth kinetics observed for 26 purified antibodies. [Figure 4] Figure 1 shows the distinct CD71 upregulation kinetics observed for 26 purified antibodies. [Diagram 5] The ten best agonist monoclones that specifically bind to Vβ17 using the SKW3 cell line variants are shown. [Figure 6] Shows that ten purified Vβ17 antibodies bind well to PBMCs. [Figure 7] The ten final candidate monoclones display different isotypes based on their hybrid parent. [Figure 8] Figure 1 shows the internalization assay used to screen the 10 final candidate antibodies. Monoclones derived from the 28B2 parent show good internalization. Monoclones derived from 28C9, which has agonistic properties, show poor internalization. Monoclones derived from the parents 28D2 and 14H7 show no internalization. [Figure 9A] Epitope binning matrix for the 10 final candidate antibodies using Octet RED966. Purified monoclonal antibodies from three different parents are classified into three different groups (Figure 9B). [Figure 9B] Epitope binning matrix for the 10 final candidate antibodies using Octet RED966. Purified monoclonal antibodies from three different parents are classified into three different groups (Figure 9B). [Figure 9C] Epitope binning matrix for the 10 final candidate antibodies using Octet RED966. Purified monoclonal antibodies from three different parents are classified into three different groups (Figure 9B). [Figure 10A] Shown are the 10 final candidate antibodies that were differentially binned compared to a commercial antibody (TCR Vβ17-PE; Beckman coulter, catalog number IM2048) that served as a positive control. [Figure 10B] Shown are the 10 final candidate antibodies that were differentially binned compared to a commercial antibody (TCR Vβ17-PE; Beckman coulter, catalog number IM2048) that served as a positive control. [Figure 10C]Shown are the 10 final candidate antibodies that were differentially binned compared to a commercial antibody (TCR Vβ17-PE; Beckman coulter, catalog number IM2048) that served as a positive control. [Figure 11] It is shown that monoclones from the same parent have the same VH sequence. The heavy chain sequences of the monoclones belonging to the three different hybrids were diverse from each other. [Figure 12] It is shown that monoclones from the same parent have the same VK sequence. The light chain sequences of the monoclones belonging to the three different hybrids were diverse from each other. [Figure 13] Twelve novel antibodies with moderate agonistic properties and good PBMC binding are shown. [Figure 14A] FIG. 1 shows that monoclones derived from the hybrid parent 23A9 were binned similarly to the positive control antibody TCRVβ17-PE. [Figure 14B] FIG. 1 shows that monoclones derived from the hybrid parent 23A9 were binned similarly to the positive control antibody TCRVβ17-PE. [Figure 14C] FIG. 1 shows that monoclones derived from the hybrid parent 23A9 were binned similarly to the positive control antibody TCRVβ17-PE. [Figure 15A] Shows that monoclones derived from parent 23A9 and the positive control TCRVβ17-PE were binned differently than monoclones derived from the other hybrid parents. [Figure 15B] Shows that monoclones derived from parent 23A9 and the positive control TCRVβ17-PE were binned differently than monoclones derived from the other hybrid parents. [Figure 15C] Shows that monoclones derived from parent 23A9 and the positive control TCRVβ17-PE were binned differently than monoclones derived from the other hybrid parents. [Figure 16] Most of the monoclones show binding to cells expressing Vβ17 without competition with the positive control TCR Vβ17.

[0046] (Detailed description) In the Background and throughout the specification, various publications, articles and patents are cited or described, and each of these references is incorporated herein by reference in its entirety. The discussion of documents, acts, materials, devices, articles and the like which has been included in the specification is for the purpose of providing a context for the present invention. Such discussion is not an admission that any or all of these items constitute part of the prior art to any invention disclosed or claimed.

[0047] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Unless otherwise defined, certain terms used herein have the meanings described herein.

[0048] It should be noted that as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly indicates otherwise.

[0049] Unless otherwise stated, any numerical values, such as concentrations or concentration ranges, described herein should be understood in all cases as being modified by the term "about." Thus, numerical values ​​typically include ±10% of the described value. For example, a concentration of 1 mg / mL typically includes 0.9 mg / mL to 1.1 mg / mL. Similarly, a concentration range of 1% to 10% (w / v) includes 0.9% (w / v) to 11% (w / v). As used herein, the use of numerical ranges expressly includes all possible subranges, all individual numerical values ​​within the range, including integers and fractions of values ​​within the range, unless the context clearly indicates otherwise.

[0050] Unless otherwise indicated, the term "at least" preceding a series of elements should be understood to refer to every element in the series.

[0051] 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 which equivalents are intended to be encompassed by the present invention.

[0052] It will be understood that as used herein, the terms "comprises," "comprising," "includes," "including," "has," "having," "contains," or "containing," or any other variation thereof, are intended to be inclusive of the stated element or elements, but not to the exclusion of other elements or elements, and are intended to be non-exclusive or open-ended. For example, a composition, mixture, process, method, article, or device that includes a list of elements is not necessarily limited to only those elements, but may include other elements not expressly listed or that are inherent to such composition, mixture, process, method, article, or device. Further, unless expressly stated to the contrary, "or" refers to an inclusive "or" and not an exclusive "or." For example, condition A or B is satisfied by one of the following: A is true (or exists) and B is false (or does not exist), A is false (or does not exist) and B is true (or exists), and both A and B are true (or exist).

[0053] As used herein, the connective term "and / or" between multiple listed elements is understood to encompass both individual and combined options. For example, when two elements are connected by "and / or," the first option refers to the first element being applicable without the second element. The second option refers to the second element being applicable without the first element. The third option refers to the first and second elements being applicable together. Any one of these options is understood to be included in the meaning and thus meets the requirements of the term "and / or" as used herein. The simultaneous applicability of two or more of the options is also understood to be included in the meaning and thus meets the requirements of the term "and / or."

[0054] As used herein, the term "consists of," or variations such as "consist of" or "consisting of," as used throughout the specification and claims, includes any listed element or elements, but indicates that no additional element or elements are added to the specified method, structure, or composition.

[0055] As used herein, the term "consists essentially of," or variations such as "consist essentially of" or "consisting essentially of," as used throughout the specification and claims, indicates the inclusion of any recited element or group of elements, optionally including any recited element or group of elements that do not materially change the basic or novel characteristics of the specified method, structure, or composition.

[0056] As used herein, "subject" refers to any animal, preferably a mammal, most preferably a human. As used herein, the term "mammal" encompasses any mammal. Examples of mammals include, but are not limited to, cows, horses, sheep, pigs, cats, dogs, mice, rats, rabbits, guinea pigs, monkeys, humans, etc. In certain embodiments, the subject is a human.

[0057] It should also be understood that the terms "about," "approximately," "generally," "substantially," and the like, used herein when referring to dimensions or features of components of the embodiments provided herein, indicate that the described dimensions / features are not precise boundaries or parameters, and do not exclude minor variations therefrom that are functionally the same or similar, as would be understood by one of ordinary skill in the art. At a minimum, such references involving numerical parameters will include variations that do not change the least significant digit using mathematical and industrial principles accepted in the art (e.g., rounding, measurement, or other systematic errors, manufacturing tolerances, etc.).

[0058] The terms "identical" or percent "identity," in the context of two or more nucleic acid or polypeptide sequences (e.g., Vβ17 antibodies and the polynucleotides encoding them, the Vβ17 polynucleotides encoding them), refer to two or more sequences or subsequences that are the same or have a specified percentage of the same amino acid residues or nucleotides when compared and aligned for maximum correspondence, as measured using one of the following sequence comparison algorithms or by visual inspection.

[0059] For sequence comparison, typically one sequence serves as a reference sequence to which test sequence is compared.When using sequence comparison algorithm, test and reference sequences are input into computer, subsequence coordinates are designated as necessary, and sequence algorithm program parameters are designated.Then, sequence comparison algorithm calculates the percent sequence identity of test sequence to reference sequence based on designated program parameters.

[0060] Optimal alignment of sequences for comparison can be determined, for example, by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), the similarity search method of Pearson & Lipman, Proc. Nat'l. Acad. Sci. USA 85:2444 (1988), computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by visual inspection (see generally Current Protocols in Molecular Biology, FMAusubel et al., eds., Current Protocols, a joint venture between Greene Publishing Associates, Inc. and John Wiley & Sons, Inc., (1995 This can be done by the method of the Supplement (Ausubel).

[0061] Examples of suitable algorithms for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms described in Altschul et al., (1990) J. Mol. Biol. 215:403-410 and Altschul et al., (1997) Nucleic Acids Res. 25:3389-3402, respectively. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence that either match when aligned with words of the same length in database sequences or meet some positive threshold score T. T is referred to as the neighborhood word score threshold (Altschul et al., supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs that contain them. The word hits are then extended in both directions along each sequence for as far as the cumulative alignment score can be increased.

[0062] For nucleotide sequences, the parameters M (reward score for a pair of matching residues, always >0) and N (penalty score for mismatching residues, always <0) are used to calculate the cumulative score. For amino acid sequences, a scoring matrix is ​​used to calculate the cumulative score. Extension of the word hits in each direction is stopped when the cumulative alignment score falls off its maximum achieved value by an amount X, when the accumulation of one or more alignments of negative scoring residues causes the cumulative score to fall below zero, or when the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a wordlength (W) of 11, an expectation (E) of 10, M=5, N=-4, and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a wordlength (W) of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 (1989)).

[0063] In addition to calculating the percent sequence identity, the BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin & Altschul, Proc. Nat'l. Acad. Sci. USA 90:5873-5787 (1993)). One measure of similarity provided by the BLAST algorithm is the minimum sum probability (P(N)), which provides an indication of the probability that a match between two nucleotide sequences or two amino acid sequences will occur by chance. For example, a nucleic acid is considered to be similar to a reference sequence if the minimum sum probability in the comparison of the test nucleic acid to the reference nucleic acid is less than about 0.1, more preferably less than about 0.01, and most preferably less than about 0.001.

[0064] A further indication that two nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid is immunologically cross-reactive with the polypeptide encoded by the second nucleic acid, as described below. Thus, a polypeptide is typically substantially identical to a second polypeptide, e.g., the two peptides differ only by conservative substitutions. Another indication that two nucleic acid sequences are substantially identical is that the two molecules hybridize to each other under stringent conditions.

[0065] As used herein, the term "polynucleotide" is also referred to interchangeably as "nucleic acid molecule," "nucleotide," or "nucleic acid," and refers to any polyribonucleotide or polydeoxyribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA. "Polynucleotide" includes, but is not limited to, single-stranded and double-stranded DNA, DNA that is a mixture of single-stranded and double-stranded regions, single-stranded and double-stranded RNA, and RNA that is a mixture of single-stranded and double-stranded regions, hybrid molecules containing DNA and RNA that may be single-stranded or more typically double-stranded, or a mixture of single-stranded and double-stranded regions. In addition, "polynucleotide" refers to triple-stranded regions that include RNA or DNA or both RNA and DNA. The term polynucleotide also includes DNA or RNA that contain one or more modified bases, and DNA or RNA with backbones modified for stability or other reasons. "Modified" bases include, for example, tritylated bases and unusual bases, such as inosine. A variety of modifications can be made to DNA and RNA. Thus, "polynucleotide" includes chemically, enzymatically, or metabolically modified forms of polynucleotides typically found in nature, as well as chemical forms having characteristics of viral and cellular DNA and RNA. "Polynucleotide" also includes relatively short nucleic acid strands, often referred to as oligonucleotides.

[0066] As used herein, the term "vector" refers to a replicon into which another nucleic acid segment may be operatively inserted to bring about the replication or expression of the segment.

[0067] As used herein, the term "host cell" refers to a cell that contains a nucleic acid molecule provided herein. A "host cell" can be any type of cell, e.g., a primary cell, a cell in culture, or a cell from a cell line. In one embodiment, a "host cell" is a cell that has been transfected with a nucleic acid molecule provided herein. In another embodiment, a "host cell" is the progeny or potential progeny of such a transfected cell. The progeny of a cell may or may not be identical to the parent cell, depending, for example, on mutations or environmental influences that may arise in subsequent generations, or on the integration of the nucleic acid molecule into the host cell genome.

[0068] As used herein, the term "expression" refers to the biosynthesis of a gene product. The term includes transcription of a gene into RNA. The term also includes translation of RNA into one or more polypeptides, and further includes all naturally occurring post-transcriptional and post-translational modifications. The expressed antibody may be present in the cytoplasm of a host cell, in an extracellular environment such as the growth medium of a cell culture, or may be anchored to the cell membrane.

[0069] As used herein, the term "peptide", "polypeptide", or "protein" can refer to a molecule composed of amino acids and can be recognized as a protein by those skilled in the art. Conventional one-letter or three-letter codes for amino acid residues are used herein. The terms "peptide", "polypeptide", and "protein" can be used interchangeably herein to refer to a polymer of amino acids of any length. The polymer can be linear or branched, can contain modified amino acids, and can be interrupted by non-amino acids. The term also encompasses amino acid polymers that are naturally modified or modified by intervention, such as disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Also included within the definition are, for example, polypeptides containing one or more analogs of an amino acid (including, for example, unnatural amino acids, etc.), as well as other modifications known in the art.

[0070] The peptide sequences described herein are written according to the usual convention with the N-terminal region of the peptide on the left and the C-terminal region on the right, although isomeric forms of amino acids are known, unless expressly indicated otherwise, it is the L-form of the amino acid that is shown.

[0071] antibody Provided herein are Vβ17 antibodies or antigen-binding fragments thereof, nucleic acids and expression vectors encoding the antibodies, recombinant cells containing the vectors, and compositions comprising the antibodies. Methods of making the antibodies and methods of using the antibodies to treat diseases are also provided. The antibodies disclosed herein have one or more desirable functional properties, including, but not limited to, high affinity binding to Vβ17 or high specificity for Vβ17. In certain embodiments, the antibodies disclosed herein have the ability to treat or prevent a disease or disorder when administered to a subject alone or in combination with other therapies.

[0072] As used herein, the term "antibody" is used in a broad sense and includes immunoglobulin or antibody molecules, including human, humanized, composite, and chimeric antibodies, as well as antibody fragments that are monoclonal or polyclonal. In general, antibodies are proteins or peptide chains that exhibit binding specificity to a specific antigen. The structure of antibodies is well known. Immunoglobulins can be assigned to five major classes (i.e., IgA, IgD, IgE, IgG, and IgM) depending on the amino acid sequence of the heavy chain constant domain. IgA and IgG are further subdivided into isotypes IgA1, IgA2, IgG1, IgG2, IgG3, and IgG4. Thus, the antibodies provided herein can be of any of the five major classes or corresponding subclasses. In certain embodiments, the antibodies provided herein are IgG1, IgG2, IgG3, or IgG4. The antibody light chains of vertebrate species can be assigned to one of two clearly distinct types, namely kappa and lambda, based on the amino acid sequence of their constant domains. Thus, the antibodies provided herein can, in certain embodiments, contain a kappa light chain constant domain. The antibodies provided herein can also, in certain embodiments, contain a lambda light chain constant domain. According to certain embodiments, the antibodies provided herein comprise heavy and / or light chain constant regions derived from a rat or human antibody. In certain embodiments, the constant regions are human constant regions.

[0073] In addition to heavy and light chain constant domains, antibodies contain an antigen-binding region composed of a light chain variable region (VL) and a heavy chain variable region (VH), each of which contains three domains (i.e., complementarity determining region 1 (CDR1), CDR2, and CDR3). "CDR" refers to one of the three hypervariable regions (HCDR1, HCDR2, or HCDR3) in the non-framework region of an immunoglobulin (Ig or antibody) VH β-sheet framework or one of the three hypervariable regions (LCDR1, LCDR2, or LCDR3) in the non-framework region of an antibody VL β-sheet framework. Thus, CDRs are variable region sequences interspersed within framework region sequences. CDR regions are well known to those skilled in the art and have been defined, for example, by Kabat as the most variable regions within antibody variable (V) domains (Kabat et al., J. Biol. Chem. 252:6609-6616 (1977); Kabat, Adv. Prot. Chem. 32:1-75 (1978)). CDR region sequences have also been structurally defined by Chothia as residues that are not part of a conserved β-sheet framework and can therefore adopt various conformations (Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). Both terms are well recognized in the art. CDR region sequences have also been defined by AbM, Contact, and IMGT. Exemplary CDR region sequences are illustrated herein, for example, in the tables provided below. The positions of CDRs within canonical antibody variable regions have been determined by comparison of numerous structures (Al-Lazikani et al., J. Mol. Biol. 273:927-948 (1997); Morea et al., Methods 20:267-279 (2000)). Because the number of residues within hypervariable regions varies in different antibodies, additional residues relative to the canonical positions are conventionally numbered with a, b, c, etc. next to the residue number in the canonical variable region numbering scheme (Al-Lazikani et al., supra (1997)).Such nomenclature is similarly well known to those of skill in the art.

[0074] The light chain variable region CDR1 domain is referred to herein interchangeably as LCDR1 or VL CDR1. The light chain variable region CDR2 domain is referred to herein interchangeably as LCDR2 or VL CDR2. The light chain variable region CDR3 domain is referred to herein interchangeably as LCDR3 or VL CDR3. The heavy chain variable region CDR1 domain is referred to herein interchangeably as HCDR1 or VH CDR1. The heavy chain variable region CDR2 domain is referred to herein interchangeably as HCDR2 or VH CDR2. The heavy chain variable region CDR1 domain is referred to herein interchangeably as HCDR3 or VH CDR3.

[0075] As used herein, the term "hypervariable region" such as VH or VL refers to the region of an antibody variable region that is hypervariable in sequence and / or forms structurally defined loops. Generally, an antibody contains six hypervariable regions, three for VH (HCDR1, HCDR2, HCDR3) and three for VL (LCDR1, LCDR2, LCDR3). Numerous delineations of hypervariable regions are in use and are encompassed herein. The "Kabat" CDRs are based on sequence variability and are the most commonly used (see, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)). "Chothia" instead refers to the location of the structural loops (see, e.g., Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). The ends of the Chothia CDR-HCDR1 loop when numbered using the Kabat numbering convention vary from H32 to H34 depending on the length of the loop (this is because the Kabat numbering scheme places insertions at H35A and H35B; if neither 35A nor 35B are present, the loop ends at 32, if only 35A is present, the loop ends at 33, and if both 35A and 35B are present, the loop ends at 34). The "AbM" hypervariable regions represent a compromise between the Kabat CDRs and the Chothia structural loops and are used by Oxford Molecular's AbM antibody modeling software (see, e.g., Martin, in Antibody Engineering, Vol. 2, Chapter 3, Springer Verlag). The "Contact" hypervariable regions are based on an analysis of available complex crystal structures.

[0076] Recently, a universal numbering system has been developed and widely adopted, the ImMunoGeneTics (IMGT) Information System® (Lafranc et al., Dev. Comp. Immunol. 27(1):55-77 (2003)). IMGT is an integrated information system dedicated to immunoglobulins (IG), T cell receptors (TR), and major histocompatibility complexes (MHC) of humans and other vertebrates. Herein, CDRs are referred to in terms of both amino acid sequence and location within the light or heavy chain. Because the "location" of the CDRs within the structure of immunoglobulin variable domains is conserved among species and occurs in structures called loops, by using a numbering system that aligns variable domain sequences according to structural features, CDR and framework residues are readily identified. This information can be used to graft and replace CDR residues from an immunoglobulin of one species into an acceptor framework, typically from a human antibody. An additional numbering system (AHon) has been developed by Honegger and Pluckthun, J. Mol. Biol. 309:657-670 (2001). Correspondence between numbering systems, including, for example, Kabat numbering and the IMGT specific numbering system, is well known to those of skill in the art (see, e.g., Kabat, supra; Chothia and Lesk, supra; Martin, supra; Lefranc et al., supra). The exemplary system presented herein combines Kabat and Chothia.

[0077] [Table 1]

[0078] The hypervariable regions may include "extended hypervariable regions" as follows: 24-36 or 24-34 (LCDR1), 46-56 or 50-56 (LCDR2), and 89-97 or 89-96 (LCDR3) in VL, and 26-35 or 26-35A (HCDR1), 50-65 or 49-65 (HCDR2), and 93-102, 94-102, or 95-102 (HCDR3) in VH. CDR sequences reflecting each of the above numbering schemes, contained in Tables 1-6, are provided herein.

[0079] The term "constant region" or "constant domain" refers to the carboxy-terminal portions of the light and heavy chains that are not directly involved in binding the antibody to an antigen, but exhibit various effector functions, such as interaction with Fc receptors. The term refers to the portion of the immunoglobulin molecule that has a more conserved amino acid sequence compared to the other portion of the immunoglobulin, the variable region, which contains the antigen-binding site. The constant region may contain the CH1, CH2, and CH3 regions of the heavy chain and the CL region of the light chain.

[0080] The term "framework" or "FR" residues are those variable region residues which flank the CDRs. FR residues are present, for example, in chimeric, humanized, human, domain, diabodies, linear, and bispecific antibodies. FR residues are variable domain residues other than the hypervariable region or CDR residues.

[0081] As used herein, the term "isolated antibody" refers to an antibody that is substantially free of other antibodies having different antigen specificities (e.g., an isolated antibody that specifically binds to Vβ17 is substantially free of antibodies that do not bind to Vβ17). In addition, an isolated antibody is substantially free of other cellular material and / or chemicals.

[0082] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies that make up the population are identical except for naturally occurring mutations that may be present in minor amounts. The monoclonal antibodies provided herein can be produced by hybridoma methods, phage display techniques, single lymphocyte gene cloning techniques, or recombinant DNA methods. For example, monoclonal antibodies can be produced by hybridomas that contain B cells obtained from a transgenic non-human animal, e.g., a transgenic mouse or rat, and have a genome that contains a human heavy chain transgene and a light chain transgene.

[0083] As used herein, the term "antigen-binding fragment" refers to, for example, a diabody, Fab, Fab', F(ab')2, Fv fragment, disulfide stabilized Fv fragment (dsFv), (dsFv) 2 , bispecific dsFv (dsFv-dsFv'), disulfide stabilized diabodies (ds diabodies), single chain antibody molecules (scFv), single domain antibodies (sdAb) scFv dimers (bivalent diabodies), multispecific antibodies formed from portions of an antibody comprising one or more CDRs, camelized single domain antibodies, nanobodies, domain antibodies, bivalent domain antibodies, or any other antibody fragment that binds to an antigen but does not comprise the complete antibody structure. An antigen-binding fragment can bind to the same antigen to which the parent antibody or parent antibody fragment binds. According to certain embodiments, the antigen-binding fragment comprises a light chain variable region, a light chain constant region, and an Fd fragment of the heavy chain. According to other particular embodiments, the antigen-binding fragment comprises Fab and F(ab').

[0084] As used herein, the term "single chain antibody" refers to a single chain antibody conventionally known in the art that contains a heavy chain variable region and a light chain variable region connected by a short peptide of about 15 to about 20 amino acids. As used herein, the term "single domain antibody" refers to a single domain antibody conventionally known in the art that contains a heavy chain variable region and a heavy chain constant region, or contains only a heavy chain variable region.

[0085] As used herein, the term "human antibody" refers to an antibody produced by a human or an antibody having an amino acid sequence corresponding to an antibody produced by a human, made using any technique known in the art. This definition of a human antibody includes intact or full-length antibodies, fragments thereof, and / or antibodies that comprise at least one human heavy and / or light chain polypeptide.

[0086] As used herein, the term "humanized antibody" refers to a non-human antibody that has been modified to increase sequence homology to that of a human antibody such that the antigen-binding properties of the antibody are retained but the antigenicity of the antibody in the human body is reduced.

[0087] As used herein, the term "chimeric antibody" refers to an antibody in which the amino acid sequences of the immunoglobulin molecules are derived from two or more species. The variable regions of both the light and heavy chains often correspond to the variable regions of an antibody derived from one species of mammal (e.g., mouse, rat, rabbit, etc.) having the desired specificity, affinity, and capacity, while the constant regions correspond to the sequences of an antibody derived from another species of mammal (e.g., human) to avoid eliciting an immune response in that species.

[0088] As used herein, the term "multispecific antibody" refers to an antibody comprising a plurality of immunoglobulin variable domain sequences, where a first immunoglobulin variable domain sequence of the plurality has binding specificity for a first epitope and a second immunoglobulin variable domain sequence of the plurality has binding specificity for a second epitope. In certain embodiments, the first and second epitopes do not overlap or do not substantially overlap. In certain embodiments, the first and second epitopes are on different antigens, e.g., on different proteins (or different subunits of a multimeric protein). In certain embodiments, the multispecific antibody comprises a third, fourth, or fifth immunoglobulin variable domain. In certain embodiments, the multispecific antibody is a bispecific antibody molecule, a trispecific antibody molecule, or a tetraspecific antibody molecule.

[0089] As used herein, the term "bispecific antibody" refers to a multispecific antibody that binds up to two epitopes or two antigens, e.g., two epitopes or antigens that are different genetic targets (e.g., Vβ17, CD69, or CD25). A bispecific antibody is characterized by a first immunoglobulin variable domain sequence that has binding specificity for a first epitope (e.g., an epitope on the Vβ17 antigen) and a second immunoglobulin variable domain sequence that has binding specificity for a second epitope. In certain embodiments, the first and second epitopes are on different antigens, e.g., on different proteins (or different subunits of a multimeric protein). In certain embodiments, a bispecific antibody comprises heavy and light chain variable domain sequences that have binding specificity for a first epitope and heavy and light chain variable domain sequences that have binding specificity for a second epitope. In certain embodiments, a bispecific antibody comprises a half antibody or fragment thereof that has binding specificity for a first epitope and a half antibody or fragment thereof that has binding specificity for a second epitope, hi certain embodiments, a bispecific antibody comprises an scFv or fragment thereof that has binding specificity for a first epitope and an scFv or fragment thereof that has binding specificity for a second epitope.

[0090] As used herein, the term "Vβ17" refers to a T cell receptor expressed in response to an immune response to cytotoxic T cells. Vβ17-expressing CD8+ T cells are generally generated in response to influenza A virus exposure in a subject. Vβ17-expressing CD8+ T cells provide a large recall in response to influenza exposure in a subject. The term "Vβ17" includes any Vβ17 variant, isoform, and species homolog that can be naturally expressed by a cell (including a T cell) or expressed on a cell transfected with a gene or cDNA encoding the polypeptide. Unless otherwise stated, preferably, Vβ17 is human Vβ17. An exemplary human Vβ17 amino acid sequence is provided by GenBank Accession No. AAB49730.1.

[0091] As used herein, an antibody that "specifically binds to Vβ17" is an antibody that is more than 1×10 -7 M or less, e.g., 1×10 -8 M or less, 5×10 -9 M or less, 1×10 -9 M or less, 5×10 -10 M or less, or 1 x 10 -10 It refers to an antibody that binds to Vβ17, preferably human Vβ17, with a KD of less than or equal to M.

[0092] The term "KD" refers to the dissociation constant, which is obtained from the ratio of Kd to Ka (i.e., Kd / Ka) and expressed as a molar concentration (M). The KD value of an antibody can be determined using methods in the art in light of the present disclosure. For example, the KD of an antibody can be determined by using surface plasmon resonance, for example, by using a biosensor system such as a Biacore® system, or by using biolayer interferometry technology such as an Octet RED96 system. The smaller the value of the KD of an antibody, the higher the affinity with which the antibody binds to the target antigen.

[0093] In one aspect, provided herein is an antibody that binds to Vβ17. In some embodiments, the antibody comprises a heavy chain variable region and a light chain variable region. In some embodiments, the Vβ17 antibody is not a single domain antibody or a nanobody. In some embodiments, the Vβ17 antibody is a humanized antibody.

[0094] In certain embodiments, provided herein is a Vβ17 antibody that comprises the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a Vβ17 antibody that comprises the VH region of any one of the antibodies described herein. In some embodiments, provided herein is a Vβ17 antibody that comprises the VL region of any one of the antibodies described herein. In some embodiments, provided herein is a Vβ17 antibody that comprises the VH region of any one of the antibodies described herein and the VL region of any one of the antibodies described herein. In some embodiments, provided herein is a Vβ17 antibody that comprises the VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a Vβ17 antibody that comprises the VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a Vβ17 antibody that comprises the VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described herein and the VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein. Representative VH and VL amino acid sequences, including the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the Vβ17 antibodies provided herein, are provided in Tables 1-6.

[0095] In some embodiments, the antibody specifically binds to Vβ17. In other embodiments, Vβ17 is present on the surface of a T cell.

[0096] In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is an IgG1, IgG2, IgG3, or IgG4 isotype. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the antibody is multivalent. In other embodiments, the antibody is capable of binding at least three antigens. In some embodiments, the antibody is capable of binding at least five antigens.

[0097] In certain embodiments, Vβ17 antibodies are provided that are intact antibodies. In other embodiments, Vβ17 antibodies are provided that are antigen-binding fragments of Vβ17 antibodies. In some embodiments, the antigen-binding fragments of Vβ17 antibodies are functional fragments.

[0098] In some embodiments, the antigen-binding fragment is a diabody. In some embodiments, the antigen-binding fragment is a Fab. In some embodiments, the antigen-binding fragment is a Fab'. In some embodiments, the antigen-binding fragment is a F(ab')2. In some embodiments, the antigen-binding fragment is an Fv fragment. In some embodiments, the antigen-binding fragment is a disulfide stabilized Fv fragment (dsFv). In some embodiments, the antigen-binding fragment is a (dsFv) 2In some embodiments, the antigen-binding fragment is a bispecific dsFv (dsFv-dsFv'). In some embodiments, the antigen-binding fragment is a disulfide-stabilized diabody (ds diabody). In some embodiments, the antigen-binding fragment is a single chain antibody molecule (scFv). In some embodiments, the antigen-binding fragment is a single domain antibody (sdAb). In some embodiments, the antigen-binding fragment is an scFv dimer (bivalent diabody). In some embodiments, the antigen-binding fragment is a multispecific antibody formed from a portion of an antibody comprising one or more CDRs. In some embodiments, the antigen-binding fragment is a camelized single domain antibody. In some embodiments, the antigen-binding fragment is a nanobody. In some embodiments, the antigen-binding fragment is a domain antibody. In some embodiments, the antigen-binding fragment is a bivalent domain antibody. In some embodiments, the antigen-binding fragment is an antibody fragment that binds to an antigen but does not comprise a complete antibody structure.

[0099] In certain embodiments, the Vβ17 antibody comprises a VH region and a VL region. In some embodiments, the Vβ17 antibody is a single chain antibody. In some embodiments, the Vβ17 antibody is a single domain antibody. In some embodiments, the Vβ17 antibody is a nanobody. In certain embodiments, the Vβ17 antibody is a VHH antibody. In certain embodiments, the Vβ17 antibody is a llama antibody. In some embodiments, the Vβ17 antibody is not a single chain antibody. In some embodiments, the Vβ17 antibody is not a single domain antibody. In some embodiments, the Vβ17 antibody is not a nanobody. In certain embodiments, the Vβ17 antibody is not a VHH antibody. In certain embodiments, the Vβ17 antibody is not a llama antibody. In some embodiments, the Vβ17 antibody is a multispecific antibody. In other embodiments, the Vβ17 is a bispecific antibody. In certain embodiments, the multispecific antibody comprises an antigen-binding fragment of a Vβ17 antibody provided herein. In other embodiments, the bispecific antibody comprises an antigen-binding fragment of a Vβ17 antibody provided herein. In some embodiments, the Vβ17 antibody is an agonist antibody. In certain embodiments, the Vβ17 antibody activates T cells. In other embodiments, the Vβ17 antibody is an antagonist antibody. In certain embodiments, the Vβ17 antibody inactivates T cells. In some embodiments, the Vβ17 antibody blocks T cell activation. In some embodiments, the Vβ17 antibody modulates T cell activity. In some embodiments, the Vβ17 antibody does not activate or inactivate T cell activity. In certain embodiments, the T cell is a human T cell.

[0100] In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences follow the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences follow the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences follow an exemplary numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences follow the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences follow the IMGT numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences follow the AbM numbering system. Exemplary sets of six CDRs (VH CDR1-3 and VL CDR1-3) of certain antibody embodiments are provided herein. Other CDR sets are contemplated and are within the scope of the antibody embodiments provided herein.

[0101] [Table 2-1]

[0102] [Table 2-2]

[0103] [Table 3]

[0104] [Table 4]

[0105]

Table 5

[0106]

Table 6

[0107]

Table 7

[0108] In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 1, 2, and 3, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 4, 5, and 6, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 7, 8, and 9, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 10, 11, and 12, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 13, 14, and 15, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 16, 17, and 18, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 19, 20, and 21, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 22, 23, and 24, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising: (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 25, 26, and 27, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 28, 29, and 30, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising: (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 31, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 32.In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 31. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having the amino acid sequence of SEQ ID NO: 32. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 31 and a VL having the amino acid sequence of SEQ ID NO: 32. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 31. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 32. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 31 and a VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 32.

[0109] In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 35, 36, and 37, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 38, 39, and 40, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 41, 42, and 43, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 44, 45, and 46, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 47, 48, and 49, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 50, 51, and 52, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 53, 54, and 55, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 56, 57, and 58, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising: (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 59, 60, and 61, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 62, 63, and 64, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising: (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 65, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 66.In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence of SEQ ID NO: 65. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence of SEQ ID NO: 66. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence of SEQ ID NO: 65 and a VL having an amino acid sequence of SEQ ID NO: 66. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 65. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 66. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 65 and a VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 66.

[0110] In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 69, 70, and 71, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 72, 73, and 74, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 75, 76, and 77, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 78, 79, and 80, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 81, 82, and 83, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 84, 85, and 86, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 87, 88, and 89, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 90, 91, and 92, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 93, 94, and 95, respectively; and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 96, 97, and 98, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 99, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 100. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 99. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having the amino acid sequence of SEQ ID NO: 100. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 99 and a VL having the amino acid sequence of SEQ ID NO: 100. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 99. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 100. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 99 and a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 100.

[0111] In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 103, 104, and 105, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 106, 107, and 108, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 109, 110, and 111, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 112, 113, and 114, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 115, 116, and 117, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 118, 119, and 120, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 121, 122, and 123, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 124, 125, and 126, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 127, 128, and 129, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 130, 131, and 132, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 133, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 134. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 133. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having the amino acid sequence of SEQ ID NO: 134. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 133 and a VL having the amino acid sequence of SEQ ID NO: 134. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 133. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 134. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 133, and a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 134.

[0112] In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 137, 138, and 139, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 140, 141, and 142, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 143, 144, and 145, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 146, 147, and 148, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 149, 150, and 151, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 152, 153, and 154, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 155, 156, and 157, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 158, 159, and 160, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising: (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 161, 162, and 163, respectively; and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 164, 165, and 166, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 167, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 168. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 167. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having the amino acid sequence of SEQ ID NO: 168. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 167 and a VL having the amino acid sequence of SEQ ID NO: 168. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 167. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 168. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 167, and a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 168.

[0113] In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 171, 172, and 173, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 174, 175, and 176, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 177, 178, and 179, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 180, 181, and 182, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 183, 184, and 185, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 186, 187, and 188, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 189, 190, and 191, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 192, 193, and 194, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising: (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 195, 196, and 197, respectively; and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 198, 199, and 200, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 201, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 202. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 201. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having the amino acid sequence of SEQ ID NO: 202. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 201 and a VL having the amino acid sequence of SEQ ID NO: 202. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 201. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 202. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 201, and a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 202.

[0114] In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 205, 206, and 207, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 208, 209, and 210, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 211, 212, and 213, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 214, 215, and 216, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 217, 218, and 219, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 220, 221, and 222, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 223, 224, and 225, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 226, 227, and 228, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising: (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 229, 230, and 231, respectively; and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 232, 233, and 234, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 235, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 236. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 235. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having the amino acid sequence of SEQ ID NO: 236. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 235 and a VL having the amino acid sequence of SEQ ID NO: 236. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 235. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 236. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 235, and a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 236.

[0115] In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 239, 240, and 241, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 242, 243, and 244, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 245, 246, and 247, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 248, 249, and 250, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 251, 252, and 253, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 254, 255, and 256, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 257, 258, and 259, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 260, 261, and 262, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 263, 264, and 265, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 266, 267, and 268, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 269, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 270. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 269. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having the amino acid sequence of SEQ ID NO: 270. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 269 and a VL having the amino acid sequence of SEQ ID NO: 270. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 269. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 270. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 269, and a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 270.

[0116] In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 273, 274, and 275, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 276, 277, and 278, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 279, 280, and 281, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 282, 283, and 284, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 285, 286, and 287, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 288, 289, and 290, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 291, 292, and 293, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 294, 295, and 296, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising: (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 297, 298, and 299, respectively; and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 300, 301, and 302, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 303, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 304. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 303. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having the amino acid sequence of SEQ ID NO: 304. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 303 and a VL having the amino acid sequence of SEQ ID NO: 304. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 303. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 304. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 303, and a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 304.

[0117] In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 307, 308, and 309, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 310, 311, and 312, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 313, 314, and 315, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 316, 317, and 318, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 319, 320, and 321, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 322, 323, and 324, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 325, 326, and 327, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 328, 329, and 330, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising: (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 331, 332, and 333, respectively; and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 334, 335, and 336, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 337, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 338. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 337. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having the amino acid sequence of SEQ ID NO: 338. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 337 and a VL having the amino acid sequence of SEQ ID NO: 338. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 337. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 338. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 337, and a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 338.

[0118] In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 341, 342, and 343, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 344, 345, and 346, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 347, 348, and 349, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 350, 351, and 352, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 353, 354, and 355, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 356, 357, and 358, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 359, 360, and 361, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 362, 363, and 364, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 365, 366, and 367, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 368, 369, and 370, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 371, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 372. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 371. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having the amino acid sequence of SEQ ID NO: 372. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 371 and a VL having the amino acid sequence of SEQ ID NO: 372. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 371. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 372. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 371, and a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 372.

[0119] In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 375, 376, and 377, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 378, 379, and 380, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 381, 382, ​​and 383, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 384, 385, and 386, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 387, 388, and 389, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 390, 391, and 392, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 393, 394, and 395, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 396, 397, and 398, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising: (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 399, 400, and 401, respectively; and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 402, 403, and 404, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 405, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 406. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 405. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having the amino acid sequence of SEQ ID NO: 406. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 405 and a VL having the amino acid sequence of SEQ ID NO: 406. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 405. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 406. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 405, and a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 406.

[0120] In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 409, 410, and 411, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 412, 413, and 414, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 415, 416, and 417, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 418, 419, and 420, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 421, 422, and 423, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 424, 425, and 426, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 427, 428, and 429, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 430, 431, and 432, respectively. In one aspect, provided herein is an antibody that binds Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 433, 434, and 435, respectively, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 436, 437, and 438, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, comprising (i) a VH comprising a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 439, and (ii) a VL comprising a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 440. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 439. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having the amino acid sequence of SEQ ID NO: 440. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having the amino acid sequence of SEQ ID NO: 439 and a VL having the amino acid sequence of SEQ ID NO: 440. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 439. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 440. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 439, and a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 440.

[0121] In another aspect, provided herein is an antibody that competes with any of the Vβ17 antibodies described herein for binding to Vβ17. In another aspect, provided herein is an antibody that binds to the same epitope as any of the Vβ17 antibodies described herein. In another aspect, provided herein is a Vβ17 antibody that binds to an epitope on Vβ17 that overlaps with the epitope on Vβ17 bound by the Vβ17 antibodies described herein.

[0122] In one embodiment, an antibody is provided that competes with a Vβ17 reference antibody for binding to Vβ17. In another embodiment, a Vβ17 antibody is provided that binds to the same Vβ17 epitope as the Vβ17 reference antibody. In another embodiment, a Vβ17 antibody is provided that binds to an epitope on Vβ17 that overlaps with the epitope on Vβ17 bound by the Vβ17 reference antibody.

[0123] In one embodiment, the Vβ17 reference antibody comprises (i) a VH having the amino acid sequence of SEQ ID NO: 31, which includes a VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; and (ii) a VL having the amino acid sequence of SEQ ID NO: 32, which includes a VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the Vβ17 reference antibody comprises (i) a VH having the amino acid sequence of SEQ ID NO: 65, the VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) a VL having the amino acid sequence of SEQ ID NO: 66, the VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the Vβ17 reference antibody comprises (i) a VH having the amino acid sequence of SEQ ID NO: 99, the VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) a VL having VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of the VL having the amino acid sequence of SEQ ID NO: 100. In one embodiment, the Vβ17 reference antibody comprises (i) a VH having the amino acid sequence of SEQ ID NO: 133, the VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) a VL having VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of the VL having the amino acid sequence of SEQ ID NO: 134.In one embodiment, the Vβ17 reference antibody comprises (i) a VH having the amino acid sequence of SEQ ID NO: 167, the VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) a VL having VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of the VL having the amino acid sequence of SEQ ID NO: 168. In one embodiment, the Vβ17 reference antibody comprises (i) a VH having the amino acid sequence of SEQ ID NO: 201, which includes a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) a VL having the amino acid sequence of SEQ ID NO: 202, which includes a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the Vβ17 reference antibody comprises (i) a VH having the amino acid sequence of SEQ ID NO: 235, the VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) a VL having the amino acid sequence of SEQ ID NO: 236, the VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the Vβ17 reference antibody comprises (i) a VH having the amino acid sequence of SEQ ID NO: 269, the VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) a VL having the amino acid sequence of SEQ ID NO: 270, the VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively.In one embodiment, the Vβ17 reference antibody comprises (i) a VH having the amino acid sequence of SEQ ID NO: 303, the VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) a VL having the amino acid sequence of SEQ ID NO: 304, the VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the Vβ17 reference antibody comprises (i) a VH having the amino acid sequence of SEQ ID NO: 337, the VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) a VL having VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of the VL having the amino acid sequence of SEQ ID NO: 338. In one embodiment, the Vβ17 reference antibody comprises (i) a VH having the amino acid sequence of SEQ ID NO: 371, which includes a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) a VL having the amino acid sequence of SEQ ID NO: 372, which includes a VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the Vβ17 reference antibody comprises (i) a VH having the amino acid sequence of SEQ ID NO: 405, the VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) a VL having the amino acid sequence of SEQ ID NO: 406, the VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively.In one embodiment, the Vβ17 reference antibody comprises (i) a VH having the amino acid sequence of SEQ ID NO: 439, the VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) a VL having the amino acid sequence of SEQ ID NO: 440, the VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively.

[0124] In some embodiments, the multispecific antibodies provided herein are diabodies, crossbodies, or multispecific antibodies obtained via controlled Fab arm exchange, such as those described in the present invention.

[0125] In some embodiments, multispecific antibodies include IgG-like molecules with complementary CH3 domains that promote heterodimer formation; recombinant IgG-like dual targeting molecules, in which the two sides of the molecule each comprise a Fab fragment or portion of a Fab fragment of at least two different antibodies; IgG fusion molecules in which a full-length IgG antibody is fused to an extra Fab fragment or portion of a Fab fragment; Fc fusion molecules in which a single chain Fv molecule or a stabilized diabody is fused to a heavy chain constant domain, Fc region, or portion thereof; Fab fusion molecules in which different Fab fragments are fused together; ScFv and diabody-based antibodies and heavy chain antibodies (e.g., domain antibodies, nanobodies) in which different single chain Fv molecules or different diabodies or different heavy chain antibodies (e.g., domain antibodies, nanobodies) are fused to each other or to another protein or carrier molecule.

[0126] In some embodiments, IgG-like molecules with complementary CH3 domain molecules include Triomab / Quadroma (Trion Pharma / Fresenius Biotech), Knobs-into-Holes (Genentech), CrossMAbs (Roche) and electrostatically tailored (Amgen), LUZ-Y (Genentech), Strand Exchange Engineered Domain body (SEEDbody) (EMD Serono), Biclonic (Merus), and DuoBody (Genmab A / S).

[0127] In some embodiments, recombinant IgG-like dual targeting molecules include Dual Targeting (DT)-Ig (GSK / Domantis), Two-in-one Antibody (Genentech), Cross-linked Mabs (Karmanos Cancer Center), mAb2 (F-Star), and CovX-body (CovX / Pfizer).

[0128] In some embodiments, IgG fusion molecules include Dual Variable Domain (DVD)-Ig (Abbott), IgG-like Bispecific (ImClone / Eli Lilly), Ts2Ab (MedImmune / AZ), and BsAb (Zymogenetics), HERCULES (Biogen Idec), and TvAb (Roche).

[0129] In some embodiments, Fc fusion molecules include ScFv / Fc fusions (Academic Institution), SCORPION (Emergent BioSolutions / Trubion, Zymogenetics / BMS), dual affinity retargeting technology (Fc-DART) (MacroGenics), and dual (ScFv) 2-Fab (National Research Center for Antibody Medicine--China) can be mentioned as an example.

[0130] In some embodiments, the Fab fusion bispecific antibody comprises an F(ab) 2 (Medarex / AMGEN), Dual-Action or Bis-Fab (Genentech), Dock-and-Lock (DNL) (ImmunoMedics), Bivalent Bispecific (Biotecnol), and Fab-Fv (UCB-Celltech). ScFv antibodies, diabody-based antibodies, and domain antibodies include, but are not limited to, Bispecific T Cell Engager (BiTE) (Micromet), Tandem Diabody (Tandab) (Affimed), Dual Affinity Retargeting Technology (DART) (MacroGenics), single chain diabodies (Academic), TCR-like antibodies (AIT, ReceptorLogics), human serum albumin ScFv fusions (Merrimack), and COMBODY (Epigen Biotech), dual targeting nanobodies (Ablynx), dual targeting heavy chain only domain antibodies.

[0131] The full-length bispecific antibodies provided herein can be generated using, for example, Fab arm exchange (or half molecule exchange) between two monospecific bivalent antibodies by introducing substitutions in the heavy chain CH3 interface in each half molecule to favor the formation of heterodimers of two antibody half molecules with different specificities, either in vitro in a cell-free environment or using co-expression. The Fab arm exchange reaction is the result of a disulfide bond isomerization reaction and dissociation-association of the CH3 domains. The heavy chain disulfide bonds in the hinge region of the monospecific parent antibody are reduced. The resulting free cysteine ​​of one of the monospecific parent antibodies forms an intra-heavy chain disulfide bond with a cysteine ​​residue of the second monospecific parent antibody molecule, while the CH3 domain of the parent antibody opens and reforms upon dissociation-association. The CH3 domain of the Fab arm can be engineered to favor heterodimer formation over homodimer formation. The resulting product is a bispecific antibody having two Fab arms or half molecules, each binding to a different epitope, e.g., an epitope on a first target and an epitope on a second target. Other methods for making multispecific antibodies are known and are contemplated.

[0132] As used herein, "homodimerization" refers to the interaction of two heavy chains with identical CH3 amino acid sequences. As used herein, "homodimer" refers to an antibody having two heavy chains with identical CH3 amino acid sequences.

[0133] As used herein, "heterodimerization" refers to the interaction of two heavy chains with non-identical CH3 amino acid sequences. As used herein, "heterodimer" refers to an antibody having two heavy chains with non-identical CH3 amino acid sequences.

[0134] A "knob-in-hole" strategy (see, for example, WO 2006 / 028936) can be used to generate full-length bispecific antibodies. Briefly, selected amino acids that form the interface of the CH3 domain in human IgG can be mutated at positions that affect CH3 domain interactions to promote heterodimerization. An amino acid with a small side chain (hole) is introduced into the heavy chain of an antibody that specifically binds to a first antigen, and an amino acid with a large side chain (knob) is introduced into the heavy chain of an antibody that specifically binds to a second antigen. After co-expression of the two antibodies, a heterodimer is formed as a result of the preferential interaction of the heavy chain with the "hole" and the heavy chain with the "knob". Exemplary pairs of CH3 substitutions that form knobs and holes are T366Y / F405A, T366W / F405W, F405W / Y407A, T394W / Y407T, T394S / Y407A, T366W / T394S, F405W / T394S, and T366W / T366S_L368A_Y407V (expressed as altered position in the first CH3 domain of the first heavy chain / altered position in the second CH3 domain of the second heavy chain).

[0135] Other strategies, such as promoting heavy chain heterodimer formation using electrostatic interactions by substituting positively charged residues on one CH3 surface and negatively charged residues on the second CH3 surface, can be used as described in U.S. Patent Application Publication No. 2010 / 0015133, U.S. Patent Application Publication No. 2009 / 0182127, U.S. Patent Application Publication No. 2010 / 028637, or U.S. Patent Application Publication No. 2011 / 0123532. In another strategy, heterodimer formation can be achieved by the following substitutions: L351Y_F405AY407V / T394W, T366I_K392M_T394W / F405A_Y407V, T366L_K392M_T394W / F405A_Y407V, L351Y_Y407A / T366A_K409F, L351Y_Y407A / T366V K409F Y407A / T366A_K409F, or T350V_L351Y_F405A_Y407V, as described in U.S. Patent Application Publication No. 2012 / 0149876 or U.S. Patent Application Publication No. 2013 / 0195849. This can be facilitated by Y407V / T350V_T366L_K392L_T394W (expressed as alteration position in the first CH3 domain of the first heavy chain / alteration position in the second CH3 domain of the second heavy chain).

[0136] In addition to the above methods, the bispecific antibodies provided herein can be generated in vitro in a cell-free environment by introducing asymmetric mutations in the CH3 regions of two monospecific homodimeric antibodies and forming a bispecific heterodimeric antibody from two parent monospecific homodimeric antibodies under reducing conditions to allow disulfide bond isomerization according to the methods described in WO 2011 / 131746. In this method, a first monospecific bivalent antibody and a second monospecific bivalent antibody are engineered to have certain substitutions in the CH3 domains that promote the stability of the heterodimer, and these antibodies are incubated together under reducing conditions sufficient to allow the cysteines in the hinge region to isomerize the disulfide bonds, thereby generating a bispecific antibody by Fab arm exchange. Optionally, the incubation conditions can be returned to non-reducing conditions. Exemplary reducing agents that may be used are 2-mercaptoethylamine (2-MEA), dithiothreitol (DTT), dithioerythritol (DTE), glutathione, tris (2-carboxyethyl) phosphine (TCEP), L-cysteine, and beta-mercaptoethanol, preferably a reducing agent selected from the group consisting of 2-mercaptoethylamine, dithiothreitol, and tris (2-carboxyethyl) phosphine. For example, incubation at a temperature of at least 20° C., in the presence of at least 25 mM 2-MEA or in the presence of at least 0.5 mM dithiothreitol, at a pH of 5 to 8, e.g., pH 7.0 or pH 7.4, for at least 90 minutes may be used.

[0137] In some embodiments, the Vβ17 antibody comprises a single chain antibody. In some embodiments, the Vβ17 antibody comprises a single domain antibody. In certain embodiments, the Vβ17 antibody comprises a nanobody. In certain embodiments, the Vβ17 antibody comprises a VHH antibody. In certain embodiments, the Vβ17 antibody comprises a llama antibody. In some embodiments, the Vβ17 antibody does not comprise a single chain antibody. In some embodiments, the Vβ17 antibody does not comprise a single domain antibody. In certain embodiments, the Vβ17 antibody does not comprise a nanobody. In certain embodiments, the Vβ17 antibody does not comprise a VHH antibody. In certain embodiments, the Vβ17 antibody does not comprise a llama antibody.

[0138] In another particular aspect, provided herein is a Vβ17 antibody or antigen-binding fragment thereof that induces antibody-dependent cell-mediated cytotoxicity (ADCC). The antibody or antigen-binding fragment thereof can, for example, induce ADCC in vitro.

[0139] In certain embodiments, the TRGV9 antibody has an EC50 of less than about 160 pM when evaluated in vitro at an effector to target cell ratio of 1:1. 50 Induce T cell dependent cytotoxicity of second cells in vitro.

[0140] In some embodiments, Vβ17 is present on the surface of a T cell. In some embodiments, Vβ17 is present on the surface of a T cell and the second target antigen is on the surface of a second cell. In some embodiments, when the multispecific antibody binds to Vβ17 on the surface of the T cell and the second target antigen on the surface of the second cell, the second cell is killed.

[0141] In some embodiments, the multispecific antibody has an EC 50 In some embodiments, the multispecific antibody has an EC50 of less than about 300 pM to induce T cell dependent cytotoxicity of a second cell in vitro. 50In some embodiments, the multispecific antibody has an EC50 of less than about 160 pM to induce T cell dependent cytotoxicity of a second cell in vitro. 50 In some embodiments, a mixture of γδ T effector cells and target cells expressing a second target antigen is used to induce γδ T cell-dependent cytotoxicity of the second cell in vitro. 50 In some embodiments, the effector cell to target cell ratio is about 0.01:1 to about 5:1. In some embodiments, the effector cell to target cell ratio is about 0.1:1 to about 2:1. In some embodiments, the effector cell to target cell ratio is about 1:1.

[0142] In certain embodiments, EC 50 is less than about 1000 pM, less than about 900 pM, less than about 800 pM, less than about 700 pM, less than about 600 pM, less than about 500 pM, less than about 400 pM, less than about 300 pM, less than about 200 pM, less than about 190 pM, less than about 180 pM, less than about 170 pM, less than about 160 pM, less than about 150 pM, less than about 140 pM, less than about 130 pM, less than about 120 pM, less than about 110 pM, less than about 100 pM, less than about 90 pM, less than about 80 pM, less than about 70 pM, less than about 60 pM, less than about 50 pM, less than about 40 pM, less than about 30 pM, less than about 20 pM, or less than about 10 pM.

[0143] In certain embodiments, the ratio of effector to target cells can be, for example, 0.01:1, 0.02:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1. In certain embodiments, the concentration of the multispecific antibody is about 0.000005 ng / mL, about 0.00005 ng / mL, about 0.0005, about 0.005 ng / mL, about 0.01 ng / mL, about 0.02 ng / mL, about 0.03 ng / mL, about 0.04 ng / mL, about 0.05 ng / mL, about 0.06 ng / mL, about 0.07 ng / mL, about 0.08 ng / mL, about 0.09 ng / mL, about 0.1 ng / mL, about 0.5 ng / mL, about 1.0 ng / mL, about 10 ng / mL, about 20 ng / mL, about 30 ng / mL, about 40 ng / mL, about 50 ng / mL, about 60 ng / mL, about 70 ng / mL, about 80 ng / mL, about 90 ng / mL, about 100 ng / mL, or about 1000 ng / mL.

[0144] In another aspect, provided herein is an antibody that competes with any of the Vβ17 antibodies described herein for binding to Vβ17. In another aspect, provided herein is an antibody that binds to the same epitope as any of the Vβ17 antibodies described herein. In another aspect, provided herein is a Vβ17 antibody that binds to an epitope on Vβ17 that overlaps with the epitope on Vβ17 bound by the Vβ17 antibody described herein. In some embodiments, the Vβ17 antibody comprises the VH CDR1, VH CDR2, and VH CDR3 of the Vβ17 antibody provided herein. In some embodiments, the Vβ17 antibody comprises the VL CDR1, VL CDR2, and VL CDR3 of the Vβ17 antibody provided herein. In some embodiments, the Vβ17 antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the Vβ17 antibody provided herein. In some embodiments, the Vβ17 antibody comprises the VH of a Vβ17 antibody provided herein. In some embodiments, the Vβ17 antibody comprises the VL of a Vβ17 antibody provided herein. In some embodiments, the Vβ17 antibody comprises the VH and VL of a Vβ17 antibody provided herein. In some embodiments, the Vβ17 antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of a Vβ17 antibody provided herein. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the Vβ17 antibody are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the Vβ17 antibody are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the Vβ17 antibody are according to the AbM numbering system.In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the Vβ17 antibody follow the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the Vβ17 antibody follow the IMGT numbering system. In certain embodiments, the Vβ17 antibody is a multispecific antibody. In some embodiments, the Vβ17 antibody is a bispecific antibody.

[0145] In another aspect, an antibody is provided that competes with a Vβ17 reference antibody for binding to Vβ17. In another aspect, a Vβ17 antibody is provided that binds to the same Vβ17 epitope as a Vβ17 reference antibody. In another aspect, a Vβ17 antibody is provided that binds to an epitope on Vβ17 that overlaps with the epitope on Vβ17 bound by a Vβ17 reference antibody. In some embodiments, the Vβ17 reference antibody comprises the VH CDR1, VH CDR2, and VH CDR3 of a Vβ17 reference antibody provided herein. In some embodiments, the Vβ17 reference antibody comprises the VL CDR1, VL CDR2, and VL CDR3 of a Vβ17 reference antibody provided herein. In some embodiments, the Vβ17 reference antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of a Vβ17 reference antibody provided herein. In some embodiments, the Vβ17 reference antibody comprises the VH of a Vβ17 reference antibody provided herein. In some embodiments, the Vβ17 reference antibody comprises the VL of a Vβ17 reference antibody provided herein. In some embodiments, the Vβ17 reference antibody comprises the VH and VL of a Vβ17 reference antibody provided herein. In some embodiments, the Vβ17 reference antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of a Vβ17 reference antibody provided herein. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the Vβ17 reference antibody are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the Vβ17 reference antibody are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the Vβ17 reference antibody are according to the AbM numbering system.In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the Vβ17 reference antibody are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the Vβ17 reference antibody are according to the IMGT numbering system. In certain embodiments, the antibody is a multispecific antibody. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the Vβ17 reference antibody is a multispecific antibody. In some embodiments, the Vβ17 reference antibody is a bispecific antibody.

[0146] In some embodiments described herein, immune effector properties of the antibodies provided herein can be enhanced or silenced by modifying the Fc by techniques known to those of skill in the art. For example, Fc effector functions such as Clq binding, complement dependent cytotoxicity (CDC), antibody-dependent cell-mediated phagocytosis (ADCP), downregulation of cell surface receptors (e.g., B cell receptor, BCR), etc. can be provided and / or controlled by modifying residues in the Fc responsible for these activities.

[0147] "Antibody-Dependent Cell-Mediated Cytotoxicity" or "ADCC" refers to a cell-mediated reaction in which nonspecific cytotoxic cells expressing Fc receptors (FcR) (e.g., Natural Killer (NK) cells, neutrophils, and macrophages) recognize bound antibody on target cells and subsequently cause lysis of the target cells.

[0148] The ability of an antibody to induce ADCC can be enhanced by engineering its oligosaccharide components. Human IgG1 or IgG3 is N-glycosylated at Asn297, where the majority of glycans are in the known biantennary G0, G0F, G1, G1F, G2, or G2F forms. Antibodies produced by non-genetically engineered CHO cells typically have a glycan fucose content of at least about 85%. Removal of core fucose from biantennary complex type oligosaccharides attached to the Fc region enhances the ADCC of the antibody through improved FcγRIIIa binding, without altering antigen binding or CDC activity. Such Abs have been reported to successfully express relatively highly defucosylated antibodies with biantennary and complex type Fc oligosaccharides using different methods, such as controlling the culture osmolarity (Konno et al., Cytotechnology 64:249-65, 2012), applying the variant CHO line Lec13 as a host cell line (Shields et al., J Biol Chem 277:26733-26740, 2002), applying the variant CHO line EB66 as a host cell line (Olivier et al., MAbs; 2(4), 2010; epub ahead of print; PMID: 20562582), applying the rat hybridoma cell line YB2 / 0 as a host cell line (Shinkawa et al., J Biol Chem 278:3466-3473, 2003), introduction of small interfering RNA specific for the alpha-1,6-fucosyltransferase (FUT8) gene (Mori et al., Biotechnol Bioeng 88:901-908, 2004), or co-expression of beta-1,4-N-acetylglucosaminyltransferase III and Golgi alpha-mannosidase II or kifunensine, a potent alpha-mannosidase I inhibitor (Ferrara et al., J Biol Chem 281:5032-5036, 2006; Ferrara et al., Biotechnol Bioeng 93:851-861, 2006; Xhou et al., Biotechnol Bioeng 99:652-65, 2008).

[0149] In some embodiments described herein, ADCC elicited by the antibodies provided herein can also be enhanced by certain substitutions in the Fc of the antibody. Exemplary substitutions are at amino acid positions 256, 290, 298, 312, 356, 330, 333, 334, 360, 378, or 430 (residue numbering according to the EU index), as described, for example, in U.S. Patent No. 6,737,056.

[0150] In some embodiments, the Vβ17 antibodies provided herein are chimeric. In some embodiments, the Vβ17 antibodies provided herein are human. In some embodiments, the Vβ17 antibodies provided herein are humanized. In certain embodiments, the Vβ17 antibodies provided herein are isolated Vβ17 antibodies. In some embodiments, the Vβ17 antigen-binding fragments provided herein are chimeric. In some embodiments, the Vβ17 antigen-binding fragments provided herein are human. In some embodiments, the Vβ17 antigen-binding fragments provided herein are humanized. In certain embodiments, the Vβ17 antigen-binding fragments provided herein are isolated Vβ17 antigen-binding fragments. In some embodiments, the Vβ17 antibodies provided herein are IgG antibodies. In some embodiments, the IgG antibodies are IgG1 antibodies. In some embodiments, the IgG antibodies are IgG2 antibodies. In some embodiments, the IgG antibodies are IgG3 antibodies. In some embodiments, the IgG antibodies are IgG4 antibodies. In some embodiments, the Vβ17 antibodies provided herein are multivalent. In some embodiments, the Vβ17 antibody is capable of binding to at least three antigens. In some embodiments, the Vβ17 antibody is capable of binding to at least four antigens. In some embodiments, the Vβ17 antibody is capable of binding to at least five antigens.

[0151] Also provided is a nucleic acid encoding an antibody provided herein. In another general aspect, a vector is provided comprising an isolated nucleic acid encoding an antibody provided herein. In another general aspect, a vector is provided comprising an isolated nucleic acid encoding an antibody provided herein. Also provided is a vector comprising a nucleic acid encoding an antibody provided herein. Also provided is a host cell comprising a vector comprising a nucleic acid encoding an antibody provided herein. Also provided is a kit comprising a vector comprising a nucleic acid encoding an antibody provided herein and packaging therefor. In another general aspect, provided herein is an isolated nucleic acid encoding a monoclonal antibody or antigen-binding fragment thereof provided herein. In certain embodiments, the antibody is a Vβ17 antibody.

[0152] It will be understood by those of skill in the art that the coding sequence for a protein can be altered (e.g., substituted, deleted, inserted, etc.) without changing the amino acid sequence of the protein. Thus, it will be understood by those of skill in the art that the nucleic acid sequences encoding the antibodies provided herein can be altered without changing the amino acid sequence of the protein.

[0153] In view of the present disclosure, any vector known to those skilled in the art can be used, such as a plasmid, cosmid, phage vector, or viral vector. In some embodiments, the vector is a recombinant expression vector, such as a plasmid. The vector can include any elements for establishing the conventional functions of an expression vector, such as a promoter, a ribosome binding element, a terminator, an enhancer, a selection marker, and an origin of replication. The promoter can be a constitutive, inducible, or reconfigurable promoter. Numerous expression vectors capable of delivering nucleic acids to cells are known in the art and can be used herein to produce antibodies or antigen-binding fragments thereof in cells. Conventional cloning techniques or artificial gene synthesis can be used to generate recombinant expression vectors according to certain embodiments. Such techniques are well known to those skilled in the art in view of the present disclosure.

[0154] Also provided is a host cell comprising an isolated nucleic acid encoding an antibody provided herein. Also provided is a host cell comprising an isolated nucleic acid encoding an antigen-binding fragment provided herein. In view of the present disclosure, any host cell known to one of skill in the art can be used for recombinant expression of an antibody or antigen-binding fragment thereof provided herein. In some embodiments, the host cell is an E. coli TG1 or BL21 cell (e.g., for expression of scFv or Fab antibodies), a CHO-DG44 or CHO-K1 cell, or a HEK293 cell (e.g., for expression of full-length IgG antibodies). According to certain embodiments, the recombinant expression vector is transformed into the host cell by conventional methods, such as chemical transfection, heat shock, or electroporation, in which the recombinant nucleic acid is stably integrated into the host cell genome for efficient expression.

[0155] Methods of producing the antibodies disclosed herein are also provided. The methods include culturing cells containing nucleic acid encoding the antibody under conditions for producing the antibody and recovering the antibody from the cells or cell culture (e.g., from the supernatant). The expressed antibody can be harvested and purified from the cells according to conventional techniques known in the art and as described herein.

[0156] Pharmaceutical Compositions In another general aspect, a pharmaceutical composition is provided, comprising the Vβ17 antibody provided herein and a pharma- ceutical acceptable carrier.In certain embodiments, the antibody is isolated.Also provided is a method for producing the pharmaceutical composition, comprising combining the antibody with a pharma- ceutical acceptable carrier to obtain the pharmaceutical composition.

[0157] In another general aspect, a pharmaceutical composition is provided, comprising a Vβ17 multispecific antibody provided herein and a pharma- ceutically acceptable carrier. In certain embodiments, the multispecific antibody is isolated. Also provided is a method of producing the pharmaceutical composition, the method comprising combining the multispecific antibody with a pharma- ceutically acceptable carrier to obtain a pharmaceutical composition. Any of the antibodies provided herein are contemplated in the pharmaceutical composition.

[0158] As used herein, the term "pharmaceutical composition" refers to a product comprising an antibody provided herein together with a pharma- ceutically acceptable carrier. The antibodies provided herein and compositions comprising them are also useful in the manufacture of medicaments for therapeutic use.

[0159] As used herein, the term "carrier" refers to any excipient, diluent, filler, salt, buffer, stabilizer, solubilizer, oil, lipid, lipid-containing vesicle, microsphere, liposomal encapsulation, or other material known in the art for use in pharmaceutical formulations. It will be understood that the characteristics of the carrier, excipient, or diluent will depend on the route of administration for a particular application. As used herein, the term "pharmaceutical acceptable carrier" refers to a non-toxic material that does not interfere with the effect of the compositions provided herein, the biological activity of the compositions provided herein. According to certain embodiments, any pharmaceutical acceptable carrier suitable for use in pharmaceutical compositions of antibodies in light of the present disclosure may be used herein.

[0160] Formulation of pharmacoactive ingredients with pharmacologic acceptable carriers is known in the art, for example, Remington: The Science and Practice of Pharmacy (e.g., 21st edition (2005) and any subsequent revisions). Non-limiting examples of additional ingredients include buffers, diluents, solvents, tonicity adjusting agents, preservatives, stabilizers, and chelating agents. One or more pharmacologic acceptable carriers can be used in the formulation of the pharmaceutical compositions provided herein.

[0161] In one embodiment, the pharmaceutical composition is a liquid formulation. A preferred example of a liquid formulation is an aqueous formulation, i.e. a formulation that contains water. The liquid formulation may include a solution, a suspension, an emulsion, a microemulsion, a gel, etc. An aqueous formulation typically contains at least 50% w / w water, or at least 60%, 70%, 75%, 80%, 85%, 90%, or at least 95% w / w water.

[0162] In one embodiment, the pharmaceutical composition can be formulated as an injectable solution that can be injected, for example, via an injection device (e.g., a syringe or an infusion pump). The injection can be delivered, for example, subcutaneously, intramuscularly, intraperitoneally, intravitreally, or intravenously.

[0163] In another embodiment, the pharmaceutical composition is a solid formulation, e.g., a freeze-dried or spray-dried composition, which can be used as is or to which the physician or patient adds solvents and / or diluents before use.Solid dosage forms can include tablets, such as compressed tablets and / or coated tablets, and capsules (e.g., hard or soft gelatin capsules).The pharmaceutical composition can also be in the form of, for example, sachets, dragees, powders, granules, lozenges, or powders for reconstitution.

[0164] The dosage form may be immediate release, in which case it may include a water soluble or water dispersible carrier, or the dosage form may be delayed release, sustained release, or modified release, in which case it may include a water insoluble polymer that controls the dissolution rate of the dosage form in the gastrointestinal tract or subcutaneously.

[0165] In other embodiments, the pharmaceutical compositions may be delivered intranasally, bucally, or sublingually.

[0166] The pH of the aqueous formulation may be from pH 3 to pH 10. In one embodiment, the pH of the formulation is from about 7.0 to about 9.5. In another embodiment, the pH of the formulation is from about 3.0 to about 7.0.

[0167] In another embodiment, the pharmaceutical composition comprises a buffering agent. Non-limiting examples of buffering agents include arginine, aspartic acid, bicine, citrate, disodium monohydrogen phosphate, fumaric acid, glycine, glycylglycine, histidine, lysine, maleic acid, malic acid, sodium acetate, sodium carbonate, sodium dihydrogen phosphate, sodium phosphate, succinate, tartaric acid, tricine, and tris(hydroxymethyl)-aminomethane, and mixtures thereof. The buffering agents, individually or collectively, may be present in a concentration of about 0.01 mg / ml to about 50 mg / ml, for example, about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific buffering agents constitute alternative embodiments.

[0168] In another embodiment, the pharmaceutical composition includes a preservative. Non-limiting examples of preservatives include benzethonium chloride, benzoic acid, benzyl alcohol, bronopol, butyl 4-hydroxybenzoate, chlorobutanol, chlorocresol, chlorhexidine, chlorphenesin, o-cresol, m-cresol, p-cresol, ethyl 4-hydroxybenzoate, imidurea, methyl 4-hydroxybenzoate, phenol, 2-phenoxyethanol, 2-phenylethanol, propyl 4-hydroxybenzoate, sodium dehydroacetate, thiomerosal, and mixtures thereof. The preservatives, individually or collectively, may be present in a concentration of about 0.01 mg / ml to about 50 mg / ml, for example, about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions including each one of these specific preservatives constitute alternative embodiments.

[0169] In another embodiment, the pharmaceutical composition comprises an isotonicity agent. Non-limiting examples of isotonicity agents include salts (such as sodium chloride), amino acids (such as glycine, histidine, arginine, lysine, isoleucine, aspartic acid, tryptophan, and threonine), alditols (such as glycerol, 1,2-propanediol propylene glycol, 1,3-propanediol, and 1,3-butanediol), polyethylene glycols (e.g., PEG400), and mixtures thereof. Another example of an isotonicity agent includes sugars. Non-limiting examples of sugars may include monosaccharides, disaccharides, or polysaccharides, or water-soluble glycans, including, for example, fructose, glucose, mannose, sorbose, xylose, maltose, lactose, sucrose, trehalose, dextran, pullulan, dextrin, cyclodextrin, alpha and beta-HPCD, soluble starch, hydroxyethyl starch, and sodium carboxymethylcellulose. Another example of an isotonicity agent is a sugar alcohol, where the term "sugar alcohol" is defined as a C(4-8) hydrocarbon having at least one -OH group. Non-limiting examples of sugar alcohols include mannitol, sorbitol, inositol, galactitol, dulcitol, xylitol, and arabitol. The isotonicity agents, individually or collectively, may be present in a concentration of about 0.01 mg / ml to about 50 mg / ml, e.g., about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific isotonicity agents constitute alternative embodiments.

[0170] In another embodiment, the pharmaceutical composition comprises a chelating agent. Non-limiting examples of chelating agents include salts of citric acid, aspartic acid, ethylenediaminetetraacetic acid (EDTA), and mixtures thereof. The chelating agents, individually or collectively, may be present in a concentration of about 0.01 mg / ml to about 50 mg / ml, e.g., about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific chelating agents constitute alternative embodiments.

[0171] In another embodiment, the pharmaceutical composition comprises a stabilizer, non-limiting examples of which include one or more aggregation inhibitors, one or more oxidation inhibitors, one or more surfactants, and / or one or more protease inhibitors.

[0172] In another embodiment, the pharmaceutical composition comprises a stabilizer, which is carboxy / hydroxycellulose and its derivatives (such as HPC, HPC-SL, HPC-L, and HPMC), cyclodextrin, 2-methylthioethanol, polyethylene glycol (such as PEG3350), polyvinyl alcohol (PVA), polyvinylpyrrolidone, salts (such as sodium chloride), sulfur-containing substances (e.g., monothioglycerol), or thioglycolic acid. The stabilizers, individually or collectively, may be present in a concentration of about 0.01 mg / ml to about 50 mg / ml, for example, about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions containing each one of these specific stabilizers constitute alternative embodiments.

[0173] In further embodiments, the pharmaceutical composition comprises one or more surfactants, preferably one surfactant, at least one surfactant, or two different surfactants. The term "surfactant" refers to any molecule or ion composed of a water-soluble (hydrophilic) portion and a fat-soluble (lipophilic) portion. The surfactant may be selected, for example, from the group consisting of anionic surfactants, cationic surfactants, nonionic surfactants, and / or zwitterionic surfactants. The surfactants, individually or collectively, may be present in a concentration of about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions comprising each one of these specific surfactants constitute alternative embodiments.

[0174] In further embodiments, the pharmaceutical compositions include one or more protease inhibitors, such as, for example, EDTA, and / or benzamidine hydrochloric acid (HCl). The protease inhibitors, individually or collectively, may be present in a concentration of from about 0.1 mg / ml to about 20 mg / ml. Pharmaceutical compositions including each one of these specific protease inhibitors constitute alternative embodiments.

[0175] In another general aspect, provided herein is a method of producing a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof provided herein, the method comprising combining the antibody or antigen-binding fragment thereof with a pharma- ceutical acceptable carrier to obtain the pharmaceutical composition.

[0176] How to use The functional activity of the antibody provided herein can be characterized by methods known in the art and as described herein.Methods for characterizing antibodies and antigen-binding fragments thereof include, but are not limited to, affinity and specificity assays, including Biacore, ELISA, and OctetRed analysis; binding assays for detecting the binding of antibodies to target cells by FACS; binding assays for detecting the binding of antibodies to target antigens on cells.According to certain embodiments, methods for characterizing antibodies and antigen-binding fragments thereof include those described below.In certain embodiments, the antibody is a Vβ17 antibody.

[0177] Also provided are methods of activating T cells that express Vβ17, the methods comprising contacting the T cells with a Vβ17 antibody provided herein, in some embodiments, the contacting results in increased CD69, CD25, and / or Granzyme B expression compared to a control T cell that expresses Vβ17.

[0178] In another general aspect, a method of inactivating a T cell expressing Vβ17 is provided, the method comprising contacting the T cell with an antibody that binds to Vβ17 as provided herein. In another general aspect, a method of blocking activation of a T cell expressing Vβ17 is provided, the method comprising contacting the T cell with an antibody that binds to Vβ17 as provided herein. In another general aspect, a method of regulating activation of a T cell expressing Vβ17 is provided, the method comprising contacting the T cell with an antibody that binds to Vβ17 as provided herein.

[0179] Also provided herein is a method of treating a disease or disorder in a subject, the method comprising administering to the subject a Vβ17 antibody provided herein. Also provided herein is a method of treating a disease or disorder in a subject, the method comprising administering to the subject a Vβ17 antigen-binding fragment provided herein. Also provided herein is a method of treating a disease or disorder in a subject, the method comprising administering to the subject a pharmaceutical composition comprising a Vβ17 antibody provided herein. Also provided herein is a method of treating a disease or disorder in a subject, the method comprising administering to the subject a pharmaceutical composition comprising a Vβ17 antigen-binding fragment provided herein.

[0180] Also provided herein is a Vβ17 antibody for use in treating a disease, and a Vβ17 antibody is provided herein. In some embodiments, the disease is caused in whole or in part by a target cell having a second target present on the surface of the target cell. In some embodiments, the subject is a human. In some embodiments, the subject is a subject in need of such treatment.

[0181] Also provided herein is the use of a Vβ17 antibody in the manufacture of a medicament for the treatment of a disease, and a Vβ17 antibody is provided herein. In some embodiments, the disease is caused in whole or in part by a target cell having a second target present on the surface of the target cell. In some embodiments, the subject is a human. In some embodiments, the subject is a subject in need of such treatment.

[0182] In some embodiments, the subject is a subject in need of such treatment. In some embodiments, the subject is a human. In certain embodiments, the subject is administered an effective amount.

[0183] As used herein, the term "effective amount" refers to the amount of an active ingredient or component that elicits a desired biological or medicinal response in a subject.

[0184] According to certain embodiments, an effective amount refers to an amount of therapy sufficient to achieve one, two, three, four or more of the following effects: (i) reducing or ameliorating the severity of the disease, disorder or condition being treated or symptoms associated therewith; (ii) shortening the duration of the disease, disorder or condition being treated or symptoms associated therewith; (iii) preventing the progression of the disease, disorder or condition being treated or symptoms associated therewith; (iv) causing regression of the disease, disorder or condition being treated or symptoms associated therewith; (v) preventing the progression or onset of the disease, disorder or condition being treated or symptoms associated therewith. (vi) preventing the recurrence of the disease, disorder or condition being treated, or symptoms associated therewith; (vii) reducing hospitalization of a subject having the disease, disorder or condition being treated, or symptoms associated therewith; (viii) shortening the length of hospitalization of a subject having the disease, disorder or condition being treated, or symptoms associated therewith; (ix) increasing the survival rate of a subject having the disease, disorder or condition being treated, or symptoms associated therewith; (xi) inhibiting or alleviating the disease, disorder or condition being treated, or symptoms associated therewith in a subject; and / or (xii) enhancing or improving the prophylactic or therapeutic efficacy of another therapy.

[0185] The effective amount or dosage may vary according to a variety of factors, such as the disease, disorder, or condition being treated, the means of administration, the target site, the physiological state of the subject (including, for example, age, weight, health condition), whether the subject is human or animal, other medications being administered, and whether the treatment is prophylactic or therapeutic. Treatment dosages are optimally titrated to optimize safety and efficacy.

[0186] According to certain embodiments, the compositions described herein are formulated to be suitable for the intended route of administration to a subject. For example, the compositions described herein can be formulated to be suitable for intravenous, subcutaneous, or intramuscular administration.

[0187] As used herein, the terms "treat", "treating" and "treatment" all refer to an improvement or amelioration of at least one measurable physical parameter associated with cancer, which may, but is not necessarily discernible in the subject. The terms "treat", "treating" and "treatment" may also refer to causing regression, preventing progression, or at least slowing the progression of a disease, disorder, or condition. In certain embodiments, "treat", "treating" and "treatment" refer to alleviating, preventing progression or onset, or shortening the duration of one or more symptoms associated with a disease, disorder, or condition, such as a tumor or, more preferably, a cancer. In certain embodiments, "treat", "treating" and "treatment" refer to preventing the recurrence of a disease, disorder, or condition. In certain embodiments, "treat", "treating" and "treatment" refer to improving the survival rate of a subject having a disease, disorder, or condition. In certain embodiments, "treat", "treating", and "treatment" refer to the elimination of a disease, disorder, or condition in a subject.

[0188] In some embodiments, the Vβ17 antibodies provided herein are used in combination with a complementary therapy.

[0189] As used herein, the term "in combination" in the context of administering two or more therapies to a subject refers to the use of two or more therapies. The use of the term "in combination" does not limit the order in which the therapies are administered to a subject. For example, a first therapy (e.g., a composition described herein) can be administered before (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 16 hours, 24 hours, 48 ​​hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks before), simultaneously, or after (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 16 hours, 24 hours, 48 ​​hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks after) administering a second therapy to a subject.

[0190] The Vβ17 antibody provided herein may also be used as an agent for detecting Vβ17-expressing cells.Accordingly, in another method, a method for detecting cells expressing Vβ17 is provided, comprising contacting the cells with the Vβ17 antibody provided herein.In certain embodiments, the detection is by ELISA.In some embodiments, the detection is by FACS analysis.A kit is also provided that includes the Vβ17 antibody provided herein and instructions for use.

[0191] Concentration and Detection Methods In one aspect, the Vβ17 antibody provided herein is used as an agent for detecting Vβ17-expressing cells.Accordingly, in another method, a method for detecting cells expressing Vβ17 is provided, comprising contacting the Vβ17 antibody provided herein with the cells.In certain embodiments, the detection is by ELISA.In some embodiments, the detection is by FACS analysis.Also provided is a kit comprising the Vβ17 antibody provided herein and instructions for use.

[0192] Enrichment, isolation, separation, purification, sorting, selection, capture, or detection, or any combination thereof, can be performed using known techniques such as beads, microfluidics, solid supports, columns, etc. For example, Vβ17 cells can be separated or visualized using known methods when bound to a Vβ17 antibody provided herein.

[0193] The Vβ17 antibodies or multispecific Vβ17 antibodies provided herein can be used to selectively enrich, isolate, separate, purify, sort, select, capture or detect Vβ17 expressing cells. The Vβ17 antibodies or multispecific Vβ17 antibodies provided herein can be utilized in a bispecific format, for example, containing a first antigen-binding domain that specifically binds to Vβ17 and a second antigen-binding domain that specifically binds to a second target. In other embodiments, the multispecific Vβ17 antibodies provided herein can be utilized in a format that further incorporates a third antigen-binding domain that specifically binds to a third antigen (e.g., in a trispecific antibody). In other embodiments, the multispecific Vβ17 antibodies provided herein can be utilized in a format that further incorporates a fourth antigen-binding domain that specifically binds to a fourth antigen (e.g., as a tetraspecific antibody).

[0194] In one aspect, provided herein is a method of enriching Vβ17 expressing cells, comprising providing a sample comprising Vβ17 expressing cells, contacting the sample with a Vβ17 antibody provided herein, and enriching the Vβ17 expressing cells bound to the Vβ17 antibody. In one aspect, provided herein is a method of isolating Vβ17 expressing cells, comprising providing a sample comprising Vβ17 expressing cells, contacting the sample with a Vβ17 antibody provided herein, and isolating the Vβ17 expressing cells bound to the Vβ17 antibody. In one aspect, provided herein is a method of isolating Vβ17 expressing cells, comprising providing a sample comprising Vβ17 expressing cells, contacting the sample with a Vβ17 antibody provided herein, and isolating the Vβ17 expressing cells bound to the Vβ17 antibody. In one aspect, provided herein is a method for purifying Vβ17 expressing cells, comprising providing a sample comprising Vβ17 expressing cells, contacting the sample with a Vβ17 antibody provided herein, and purifying Vβ17 expressing cells bound to the Vβ17 antibody. In one aspect, provided herein is a method for selecting Vβ17 expressing cells, comprising providing a sample comprising Vβ17 expressing cells, contacting the sample with a Vβ17 antibody provided herein, and selecting Vβ17 expressing cells bound to the Vβ17 antibody. In one aspect, provided herein is a method for selecting Vβ17 expressing cells, comprising providing a sample comprising Vβ17 expressing cells, contacting the sample with a Vβ17 antibody provided herein, and selecting Vβ17 expressing cells bound to the Vβ17 antibody. In one aspect, provided herein is a method for capturing Vβ17-expressing cells, comprising providing a sample comprising Vβ17-expressing cells, contacting the sample with a Vβ17 antibody provided herein, and capturing Vβ17-expressing cells bound to the Vβ17 antibody. In one aspect, provided herein is a method for detecting Vβ17-expressing cells, comprising providing a sample comprising Vβ17-expressing cells, contacting the sample with a Vβ17 antibody provided herein, and detecting Vβ17-expressing cells bound to the Vβ17 antibody.

[0195] In one aspect, provided herein is a method of enriching Vβ17 expressing cells, comprising contacting a Vβ17 expressing cell with a Vβ17 antibody provided herein, and enriching the Vβ17 expressing cells bound to the Vβ17 antibody. In one aspect, provided herein is a method of isolating a Vβ17 expressing cell, comprising contacting a Vβ17 expressing cell with a Vβ17 antibody provided herein, and isolating the Vβ17 expressing cells bound to the Vβ17 antibody. In one aspect, provided herein is a method of separating a Vβ17 expressing cell, comprising contacting a Vβ17 expressing cell with a Vβ17 antibody provided herein, and isolating the Vβ17 expressing cells bound to the Vβ17 antibody. In one aspect, provided herein is a method of purifying a Vβ17 expressing cell, comprising contacting a Vβ17 expressing cell with a Vβ17 antibody provided herein, and purifying the Vβ17 expressing cells bound to the Vβ17 antibody. In one aspect, provided herein is a method for selecting Vβ17 expressing cells, comprising contacting a Vβ17 expressing cell with a Vβ17 antibody provided herein and selecting a Vβ17 expressing cell bound to the Vβ17 antibody. In one aspect, provided herein is a method for selecting a Vβ17 expressing cell, comprising contacting a Vβ17 expressing cell with a Vβ17 antibody provided herein and selecting a Vβ17 expressing cell bound to the Vβ17 antibody. In one aspect, provided herein is a method for capturing a Vβ17 expressing cell, comprising contacting a Vβ17 expressing cell with a Vβ17 antibody provided herein and capturing a Vβ17 expressing cell bound to the Vβ17 antibody. In one aspect, provided herein is a method for detecting a Vβ17 expressing cell, comprising contacting a Vβ17 expressing cell with a Vβ17 antibody provided herein and detecting a Vβ17 expressing cell bound to the Vβ17 antibody.

[0196] In one aspect, provided herein is a method of enriching Vβ17 expressing cells, comprising contacting a Vβ17 expressing cell with a Vβ17 antibody provided herein, and enriching the Vβ17 expressing cell based on the binding of the Vβ17 expressing cell to the Vβ17 antibody. In one aspect, provided herein is a method of isolating a Vβ17 expressing cell, comprising contacting a Vβ17 expressing cell with a Vβ17 antibody provided herein, and isolating the Vβ17 expressing cell based on the binding of the Vβ17 expressing cell to the Vβ17 antibody. In one aspect, provided herein is a method of separating a Vβ17 expressing cell, comprising contacting a Vβ17 expressing cell with a Vβ17 antibody provided herein, and isolating the Vβ17 expressing cell based on the binding of the Vβ17 expressing cell to the Vβ17 antibody. In one aspect, provided herein is a method for purifying a Vβ17 expressing cell, comprising contacting a Vβ17 expressing cell with a Vβ17 antibody provided herein, and purifying the Vβ17 expressing cell based on the binding of the Vβ17 expressing cell to the Vβ17 antibody. In one aspect, provided herein is a method for selecting a Vβ17 expressing cell, comprising contacting a Vβ17 expressing cell with a Vβ17 antibody provided herein, and selecting the Vβ17 expressing cell based on the binding of the Vβ17 expressing cell to the Vβ17 antibody. In one aspect, provided herein is a method for selecting a Vβ17 expressing cell, comprising contacting a Vβ17 expressing cell with a Vβ17 antibody provided herein, and selecting the Vβ17 expressing cell based on the binding of the Vβ17 expressing cell to the Vβ17 antibody. In one aspect, provided herein is a method for capturing Vβ17 expressing cells, comprising contacting a Vβ17 expressing cell with a Vβ17 antibody provided herein, and capturing the Vβ17 expressing cell based on the binding of the Vβ17 expressing cell to the Vβ17 antibody. In one aspect, provided herein is a method for detecting a Vβ17 expressing cell, comprising contacting a Vβ17 expressing cell with a Vβ17 antibody provided herein, and detecting the Vβ17 expressing cell based on the binding of the Vβ17 expressing cell to the Vβ17 antibody.

[0197] In certain embodiments of the method, the Vβ17 expressing cells are T cells. In some embodiments of the method, the Vβ17 expressing cells are in a population of cells. In some embodiments of the method, the Vβ17 expressing cells are in a population of lymphocytes. In some embodiments of the method, the Vβ17 expressing cells are in a population of T cells. In some embodiments of the method, the Vβ17 expressing cells are provided as a population of cells. In some embodiments of the method, the Vβ17 expressing cells are provided as a population of lymphocytes. In some embodiments of the method, the Vβ17 expressing cells are provided as a population of T cells. In some embodiments of the method, the Vβ17 expressing cells are provided as a sample comprising a population of cells. In some embodiments of the method, the Vβ17 expressing cells are provided as a sample comprising a population of lymphocytes. In some embodiments of the method, the Vβ17 expressing cells are provided as a sample comprising a population of T cells. In some embodiments of the method, the sample is a blood sample. In some embodiments of the method, the sample is a tissue sample. In some embodiments of the method, the sample is a tissue culture sample.

[0198] In some embodiments of the method, the Vβ17 antibody is a multispecific Vβ17 antibody provided herein. In some embodiments of the method, the Vβ17 antibody is a bispecific Vβ17 antibody provided herein. In some embodiments of the method, the Vβ17 antibody is a trispecific Vβ17 antibody provided herein. In some embodiments of the method, the Vβ17 antibody is a tetraspecific Vβ17 antibody provided herein. In certain embodiments, the Vβ17 antibody specifically binds to Vβ17. In one embodiment, the multispecific Vβ17 antibody comprises (a) a first binding domain that binds to Vβ17 and (b) a second binding domain that binds to a second target (e.g., a target that is not Vβ17). In one embodiment, the multispecific Vβ17 antibody comprises (a) a first binding domain that binds Vβ17, (b) a second binding domain that binds a second target (e.g., a target that is not Vβ17), and (c) a third binding domain that binds a third target (e.g., a target that is not Vβ17). In one embodiment, the multispecific Vβ17 antibody comprises (a) a first binding domain that binds Vβ17, (b) a second binding domain that binds a second target (e.g., a target that is not Vβ17), (c) a third binding domain that binds a third target (e.g., a target that is not Vβ17), and (d) a fourth binding domain that binds a fourth target (e.g., a target that is not Vβ17). In one embodiment, the multispecific Vβ17 antibody comprises (a) a first binding domain that specifically binds Vβ17, and (b) a second binding domain that specifically binds a second target (e.g., a target that is not Vβ17). In one embodiment, the multispecific Vβ17 antibody comprises (a) a first binding domain that specifically binds to Vβ17, (b) a second binding domain that specifically binds to a second target (e.g., a target that is not Vβ17), and (c) a third binding domain that specifically binds to a third target (e.g., a target that is not Vβ17).In one embodiment, a multispecific Vβ17 antibody comprises (a) a first binding domain that specifically binds to Vβ17, (b) a second binding domain that specifically binds to a second target (e.g., a target that is not Vβ17), (c) a third binding domain that specifically binds to a third target (e.g., a target that is not Vβ17), and (d) a fourth binding domain that specifically binds to a fourth target (e.g., a target that is not Vβ17).

[0199] In certain embodiments of the methods provided herein, the methods use multi-marker detection. In some embodiments, the multi-marker detection uses a multi-specific Vβ17 antibody provided herein. In some embodiments, the multi-marker detection uses a bi-specific Vβ17 antibody provided herein. In some embodiments, the multi-marker detection uses a tri-specific Vβ17 antibody provided herein. In some embodiments, the multi-marker detection uses a tetra-specific Vβ17 antibody provided herein.

[0200] In certain embodiments of the methods provided herein, the method is included as a step in a T cell manufacturing process. In certain embodiments, the cell is a CAR-T cell. In certain embodiments of the methods provided herein, the method is included as a step in a T cell engineering process.

[0201] In certain embodiments of the methods provided herein, the methods are included as steps in a diagnostic method. In certain embodiments of the methods provided herein, the methods are included as steps in a method for quantifying Vβ17-expressing T cells.

[0202] In certain embodiments of the methods provided herein, the methods further comprise expanding the enriched, isolated, separated, purified, sorted, selected, captured, or detected Vβ17-expressing cells. In certain embodiments, the expansion is in vitro. In certain embodiments, the expansion is in vivo. In certain embodiments of the methods provided herein, the methods further comprise growing the enriched, isolated, separated, purified, sorted, selected, captured, or detected Vβ17-expressing cells. In certain embodiments, the growth is in vitro. In certain embodiments, the growth is in vivo. In certain embodiments of the methods provided herein, the methods further comprise quantitating the enriched, isolated, separated, purified, sorted, selected, captured, or detected Vβ17-expressing cells.

[0203] Embodiment The present invention provides the following non-limiting embodiments. In one set of embodiments, the following is provided: A1. An antibody that binds to Vβ17, (1) (i) a VH having the amino acid sequence of SEQ ID NO: 31, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having the amino acid sequence of SEQ ID NO: 32, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (2) (i) a VH having an amino acid sequence of SEQ ID NO: 65, the VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 66, the VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively; (3) (i) a VH having an amino acid sequence of SEQ ID NO: 99, the VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 100, the VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively; (4) (i) a VH having an amino acid sequence of SEQ ID NO: 133, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 134, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (5) (i) a VH having an amino acid sequence of SEQ ID NO: 167, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 168, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (6) (i) a VH having an amino acid sequence of SEQ ID NO: 201, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 202, the VL having a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (7) (i) a VH having an amino acid sequence of SEQ ID NO: 235, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 236, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (8) (i) a VH having an amino acid sequence of SEQ ID NO: 269, the VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 270, the VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively; (9) (i) a VH having an amino acid sequence of SEQ ID NO: 303, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 304, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (10) (i) a VH having an amino acid sequence of SEQ ID NO: 337, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 338, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (11) (i) a VH having the amino acid sequence of SEQ ID NO: 371, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having the amino acid sequence of SEQ ID NO: 372, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (12) (i) a VH having an amino acid sequence of SEQ ID NO: 405, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 406, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; or (13) An antibody comprising: (i) a VH having an amino acid sequence of SEQ ID NO: 439, the VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 440, the VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. A2. The antibody described in embodiment A1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Kabat numbering system. A3. The antibody described in embodiment A1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Chothia numbering system. A4. The antibody described in embodiment A1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the AbM numbering system. A5. The antibody described in embodiment A1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Contact numbering system. A6. The antibody described in embodiment A1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the IMGT numbering system. A7. The antibody according to any one of embodiments A1 to A6, wherein the antibody is a humanized antibody. A8. The antibody according to any one of embodiments A1 to A7, wherein the antibody is an IgG antibody. A9. The antibody described in embodiment A8, wherein the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. A10. The antibody of any one of embodiments A1 to A9, wherein the antibody comprises a kappa light chain. A11. The antibody of any one of embodiments A1 to A9, wherein the antibody comprises a lambda light chain. A12. The antibody according to any one of embodiments A1 to A11, wherein the antibody is a monoclonal antibody. A13. An antibody according to any one of embodiments A1 to A12, wherein the antibody binds to the Vβ17 antigen. A14. An antibody according to any one of embodiments A1 to A12, wherein the antibody binds to the Vβ17 epitope. A15. The antibody according to any one of embodiments A1 to A14, wherein the antibody specifically binds to Vβ17. A16. An antibody described in any one of embodiments A1 to A15, wherein VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form a binding site for the Vβ17 antigen. A17. An antibody described in any one of embodiments A1 to A15, wherein VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form a binding site for an epitope of Vβ17. A18. The antibody of any one of embodiments A1 to A17, wherein Vβ17 is present on the surface of a T cell. A19. The antibody of any one of embodiments A1 to A18, wherein the antibody is multivalent. A20. The antibody of embodiment A19, wherein the antibody is capable of binding to at least three antigens. A21. The antibody of embodiment A19, wherein the antibody is capable of binding to at least four antigens. A22. The antibody of embodiment A19, wherein the antibody is capable of binding to at least five antigens. A23. The antibody according to any one of embodiments A1 to A22, wherein the antibody is a multispecific antibody. A24. The antibody of embodiment A23, wherein the antibody is a bispecific antibody. A25. The antibody of embodiment A23, wherein the antibody is a trispecific antibody. A26. The antibody of embodiment A23, wherein the antibody is a tetraspecific antibody. A27. A nucleic acid encoding the antibody according to any one of embodiments A1 to A26. A28. A vector comprising a nucleic acid according to embodiment A27. A29. A host cell comprising the vector described in embodiment A28. A30. A kit comprising a vector according to embodiment A28 and a package therefor. A31. A kit comprising an antibody according to any one of embodiments A1 to A26 and a package therefor. A32. A method for directing T cells expressing Vβ17 to a target cell, comprising contacting the target cell with a Vβ17 antibody described in any one of embodiments A1 to A26, wherein a second target is present on the surface of the target cell, and the contacting directs the T cells to the target cell. A33. A method for inhibiting the growth or proliferation of a target cell, comprising contacting a Vβ17 antibody described in any one of embodiments A1 to A26 with a target cell having a second target present on the surface of the target cell, wherein the contacting is in the presence of T cells expressing Vβ17, and wherein the contacting results in inhibition of the growth or proliferation of the target cell. A34. A method for eliminating target cells in a subject, comprising contacting a Vβ17 antibody described in any one of embodiments A1 to A26 with a target cell having a second target present on the surface of the target cell, wherein the contacting is in the presence of T cells expressing Vβ17, and wherein the contacting results in elimination of the target cell.

[0204] In one set of embodiments, the following is provided: B1. A pharmaceutical composition comprising an antibody that binds to Vβ17 and a pharma- ceutically acceptable carrier. B2. An antibody that binds to Vβ17 (1) (i) a VH having the amino acid sequence of SEQ ID NO: 31, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having the amino acid sequence of SEQ ID NO: 32, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (2) (i) a VH having an amino acid sequence of SEQ ID NO: 65, the VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 66, the VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively; (3) (i) a VH having an amino acid sequence of SEQ ID NO: 99, the VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 100, the VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively; (4) (i) a VH having an amino acid sequence of SEQ ID NO: 133, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 134, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (5) (i) a VH having an amino acid sequence of SEQ ID NO: 167, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 168, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (6) (i) a VH having an amino acid sequence of SEQ ID NO: 201, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 202, the VL having a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (7) (i) a VH having an amino acid sequence of SEQ ID NO: 235, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 236, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (8) (i) a VH having an amino acid sequence of SEQ ID NO: 269, the VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 270, the VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively; (9) (i) a VH having an amino acid sequence of SEQ ID NO: 303, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 304, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (10) (i) a VH having an amino acid sequence of SEQ ID NO: 337, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 338, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (11) (i) a VH having the amino acid sequence of SEQ ID NO: 371, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having the amino acid sequence of SEQ ID NO: 372, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (12) (i) a VH having an amino acid sequence of SEQ ID NO: 405, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 406, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; or (13) A pharmaceutical composition comprising: (i) a VH having an amino acid sequence of SEQ ID NO: 439, the VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 440, the VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. B3. The pharmaceutical composition of embodiment B2, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Kabat numbering system. B4. The pharmaceutical composition of embodiment B2, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Chothia numbering system. B5. The pharmaceutical composition of embodiment B2, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the AbM numbering system. B6. The pharmaceutical composition of embodiment B2, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Contact numbering system. B7. The pharmaceutical composition of embodiment B2, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the IMGT numbering system. B8. The pharmaceutical composition of any one of embodiments B1 to B7, wherein the antibody is a humanized antibody. B9. The pharmaceutical composition of any one of embodiments B1 to B8, wherein the antibody is an IgG antibody. B10. The pharmaceutical composition of embodiment B9, wherein the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. B11. The pharmaceutical composition of any one of embodiments B1-B10, wherein the antibody comprises a kappa light chain. B12. The pharmaceutical composition of any one of embodiments B1-B11, wherein the antibody comprises a lambda light chain. B13. The pharmaceutical composition of any one of embodiments B1 to B12, wherein the antibody is a monoclonal antibody. B14. The pharmaceutical composition of any one of embodiments B1-B13, wherein the antibody binds to the Vβ17 antigen. B15. The pharmaceutical composition of any one of embodiments B1-B13, wherein the antibody binds to the Vβ17 epitope. B16. The pharmaceutical composition of any one of embodiments B1-B15, wherein the antibody specifically binds to Vβ17. B17. The pharmaceutical composition of any one of embodiments B1 to B16, wherein VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form the binding site for Vβ17 antigen. B18. The pharmaceutical composition of any one of embodiments B1 to B16, wherein VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form a binding site for an epitope of Vβ17. B19. The pharmaceutical composition of any one of embodiments B1-B18, wherein Vβ17 is present on the surface of a T cell. B20. The pharmaceutical composition of any one of embodiments B1-B19, wherein the antibody is multivalent. B21. The pharmaceutical composition of embodiment B20, wherein the antibody is capable of binding to at least three antigens. B22. The pharmaceutical composition of embodiment B20, wherein the antibody is capable of binding to at least four antigens. B23. The pharmaceutical composition of embodiment B20, wherein the antibody is capable of binding to at least five antigens. B24. The pharmaceutical composition of any one of embodiments B1 to B23, wherein the antibody is a multispecific antibody. B25. The pharmaceutical composition of embodiment B24, wherein the antibody is a bispecific antibody. B26. The pharmaceutical composition of embodiment B24, wherein the antibody is a trispecific antibody. B27. The pharmaceutical composition of embodiment B24, wherein the antibody is a tetraspecific antibody. B28. A method for producing a pharmaceutical composition according to any one of embodiments B1 to B27, comprising combining an antibody with a pharma- ceutically acceptable carrier to obtain a pharmaceutical composition.

[0205] In one set of embodiments, the following is provided: C1. A method for treating a disease in a subject, comprising administering to the subject an effective amount of an antibody that binds to Vβ17, wherein the disease is caused in whole or in part by a target cell having a second target present on the surface of the target cell. C2. An antibody that binds to Vβ17 (1) (i) a VH having the amino acid sequence of SEQ ID NO: 31, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having the amino acid sequence of SEQ ID NO: 32, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (2) (i) a VH having an amino acid sequence of SEQ ID NO: 65, the VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 66, the VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively; (3) (i) a VH having an amino acid sequence of SEQ ID NO: 99, the VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 100, the VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively; (4) (i) a VH having an amino acid sequence of SEQ ID NO: 133, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 134, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (5) (i) a VH having an amino acid sequence of SEQ ID NO: 167, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 168, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (6) (i) a VH having an amino acid sequence of SEQ ID NO: 201, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 202, the VL having a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (7) (i) a VH having an amino acid sequence of SEQ ID NO: 235, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 236, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (8) (i) a VH having an amino acid sequence of SEQ ID NO: 269, the VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 270, the VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively; (9) (i) a VH having an amino acid sequence of SEQ ID NO: 303, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 304, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (10) (i) a VH having an amino acid sequence of SEQ ID NO: 337, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 338, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (11) (i) a VH having the amino acid sequence of SEQ ID NO: 371, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having the amino acid sequence of SEQ ID NO: 372, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; (12) (i) a VH having an amino acid sequence of SEQ ID NO: 405, the VH CDR1, the VH CDR2, and the VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2, and the VH CDR3, respectively; and (ii) a VL having an amino acid sequence of SEQ ID NO: 406, the VL CDR1, the VL CDR2, and the VL CDR3 having the amino acid sequences of the VL CDR1, the VL CDR2, and the VL CDR3, respectively; or (13) The method of embodiment C1, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 439; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 440. C3. The method of embodiment C2, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Kabat numbering system. C4. The method of embodiment C2, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Chothia numbering system. C5. The method of embodiment C2, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the AbM numbering system. C6. The method of embodiment C2, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the Contact numbering system. C7. The method of embodiment C2, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are according to the IMGT numbering system. C8. The method of any one of embodiments C1-C7, wherein the antibody is a humanized antibody. C9. The method of any one of embodiments C1-C8, wherein the antibody is an IgG antibody. C10. The method of embodiment C9, wherein the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. C11. The method of any one of embodiments C1-C10, wherein the antibody comprises a kappa light chain. C12. The method of any one of embodiments C1-C10, wherein the antibody comprises a lambda light chain. C13. The method of any one of embodiments C1-C12, wherein the antibody is a monoclonal antibody. C14. The method of any one of embodiments C1-C13, wherein the antibody binds to the Vβ17 antigen. C15. The method of any one of embodiments C1-C13, wherein the antibody binds to the Vβ17 epitope. C16. The method of any one of embodiments C1-C15, wherein the antibody specifically binds to Vβ17. C17. The method of any one of embodiments C1 to C16, wherein VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form the binding site for Vβ17 antigen. C18. The method of any one of embodiments C1 to C16, wherein VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form a binding site for an epitope of Vβ17. C19. The method of any one of embodiments C1-C18, wherein Vβ17 is present on the surface of a T cell. C20. The method of any one of embodiments C1-C19, wherein the antibody is multivalent. C21. The method of embodiment C20, wherein the antibody is capable of binding to at least three antigens. C22. The method of embodiment C20, wherein the antibody is capable of binding to at least four antigens. C23. The method of embodiment C20, wherein the antibody is capable of binding to at least five antigens. C24. The method of any one of embodiments C1-C23, wherein the antibody is a multispecific antibody. C25. The method of embodiment C24, wherein the antibody is a bispecific antibody. C26. The method of embodiment C24, wherein the antibody is a trispecific antibody. C27. The method of embodiment C24, wherein the antibody is a tetraspecific antibody. C28. The method of any one of embodiments C1-C27, wherein the subject is a human. C29. The method of any one of embodiments C1-C27, wherein the subject is in need of said treatment. C30. A method of activating a T cell that expresses Vβ17, comprising contacting the T cell with an antibody of any one of embodiments C1 to C29. C31. The method of embodiment C30, wherein the contacting results in increased CD69, CD25, and / or Granzyme B expression relative to a control T cell expressing Vβ17. C32. A process for producing an antibody that binds to two or more target molecules, the process comprising the steps of: obtaining a first binding domain that binds to Vβ17 present on a T cell; obtaining a second binding domain that binds to a second target on the surface of the target cell; and providing an antibody that binds to Vβ17 present on a T cell and the second target on the surface of the target cell. C33. The process of embodiment C32, wherein the step of obtaining a second binding domain that binds to a second target on the surface of a target cell is repeated n times, and further comprising n steps of providing a first binding domain that binds to Vβ17 present on a T cell and n target molecules, where n is at least 2.

[0206] Exemplary antibodies that bind to Vβ17 are provided in the Examples herein.

[0207] Exemplary binding agents that bind to Vβ17 are provided herein, eg, in the Examples and Tables 1-6.

[0208] Specific embodiments of the present invention are described herein. Upon reading the foregoing description, it is expected that variations of the disclosed embodiments may become apparent to those skilled in the art, and such variations may be adopted as necessary. It is therefore intended that the present invention be practiced otherwise than as specifically described herein, and that the present invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto, as permitted by applicable law. Moreover, any combination of the above elements in all possible these variations is encompassed herein, unless otherwise noted herein or the context clearly contradicts. Many embodiments of the present invention have been described. However, it will be understood that various modifications may be made without departing from the spirit and scope of the present invention. Thus, the description in the Examples section is intended to illustrate, rather than limit, the scope of the invention as recited in the claims. EXAMPLES

[0209] Example 1: Antibody that binds to Vβ17 1.1: Identification of Vβ17 monoclones A cell-based approach was used to identify Vβ17-specific monoclones.

[0210] Mice were tolerized with neonatal NS0-WT cells and then transfected with TCRVα10.2 * They were immunized once a week for three boosts with the Vβ17.2-expressing NS0 cell line.

[0211] High titers were obtained by inducing the expression of three mutants of the SKW3 cell line [SKW3-1(Vα10 * Vβ17), SKW3-2 (Vα12 * Vβ17), SKW3-3(Vα10 * Vβ7 / 9)] was used to examine the specificity for Vβ17.2.

[0212] Several monoclones binding to Vβ17 were identified by flow cytometry using various cell lines and primary cells as shown in Figure 1. Anti-TCR Vβ17-PE Ab, Beckman Coulter, Catalog No. IM2048 was used as a positive control. Goat anti-mouse IgG PE, Southern Biotech, Catalog No. 1030-09, E2518-RJ69Y was used as a negative control.

[0213] Example 2: Evaluation of Vβ17 antibody properties 2.1: Proliferation and activation To test the proliferation of Vβ17+ cells, 96-well ELISA plates were coated with 10 μg / mL of Vβ17 antibody or control antibody (B17B21) and incubated for 24 h. PBMCs were thawed and labeled with Cell trace violet to track proliferation. 0.5M PBMC cells / well / 200 μl of 10% RPMI medium (without IL-2) was incubated at 37 °C for 24 h at 4 °C for 1 h at 2 °C. 2Incubated for 24 hours in an incubator. Cells were transferred from 96-well to 48-well culture plates containing 200 μl of 10% RPMI medium (without IL-2). CTV dilutions were examined for proliferation and activation status using markers: CD25, CD69 and CD71.

[0214] Seven parent-derived monoclones exhibited good agonistic properties, as shown in Figure 2. Twenty-six selected monoclones with good agonistic properties were picked for purification.

[0215] Different growth kinetics were observed for the 26 purified antibodies. As shown in Figure 3, monoclones derived from the parents 28B2, 28C9 and 28D2 showed good growth and were picked for further assays.

[0216] Differential CD71 upregulation was observed for the 26 purified antibodies. As shown in Figure 4, monoclones derived from the parents 28B2, 28C9 and 28D2 showed good CD71 upregulation and were picked for further assays.

[0217] 2.2:Vβ17 binding The 10 best agonist monoclones binding to Vβ17 were evaluated using the SKW3 cell line variants. As shown in Figure 5, 10 purified antibodies from three different parents bound well to SKW3-1 and 2 cell lines, but not to SKW3-3 cells, which do not express Vβ17. The 14H7 parental purified antibody bound poorly to the SKW3-2 cell line and was included as a negative control.

[0218] Ten selected purified monoclones were evaluated for binding to PBMCs. As shown in Figure 6, ten purified antibodies belonging to three different parents bound well to T cells on PBMCs.

[0219] These 10 finalist monoclones differ in isotype based on their hybrid parent as shown in Figure 7. Purified monoclonal antibodies from the three different parents have different isotypes: 28D2 has IgG1, 28B2 has IgG2a, and 28C9 has IgG2b.

[0220] 2.3: Vβ17 antibody internalization The 10 final candidate antibodies were screened using an internalization assay. MMAF and antibodies were each administered at 50 nM concentration to 5000 cells / well / 50 ul, along with Ab control, MMAF control and 7 点目 MMAF antibodies were added at 3-fold dilutions up to 100%. MMAF antibodies were incubated with cells for 20 minutes and assays were performed in duplicate. Plates were incubated at 37°C for 96 hours after which Cell Titre Glo was added to the plates. Luminescence was read on a TECAN SPARK and % viability was calculated using the formula MMAF+Ab / MMAF X 100. Data was plotted in GraphPad Prism.

[0221] As shown in Figure 8, monoclones derived from the 28B2 parent show good internalization. Monoclones derived from the parent 28C9, which has very good agonistic properties, show little internalization. Monoclones derived from the parents 28D2 and 14H7 show no internalization.

[0222] Example 3: Epitope binning of Vβ17 monoclones Epitope binning helped to separate the final monoclones into distinct epitope-recognition groups and antibodies that recognized epitopes distinct from those of the commercially available antibodies. Differences in epitope recognition were supported by the diversity of V gene sequences.

[0223] Epitope binning matrix for the 10 final candidate antibodies using Octet RED96 showed three distinct specificities as shown in Figures 9A-9C. Antibody 1 was loaded onto an anti-mouse IgG Fc capture (AMC) sensor and then probed with antigen (TCRVα10.2 *After binding to Vβ17 huFc, they were run on the antibody 2 panel. Purified monoclonal antibodies from three different parents were binned into three different groups.

[0224] Furthermore, the 10 final candidate antibodies were binned differently compared to a commercial positive control antibody as assessed using Octet RED96. As shown in Figures 10A-10C, the positive control antibody TCRVb17-PE (Beckman coulter, Catalog No.: IM2048) was binned differently from the 10 final candidate antibodies.

[0225] Monoclones from the same parent have the same VH sequence, as shown in Figure 11. The heavy chain sequences of monoclones belonging to the three different hybrids were diverse from each other.

[0226] Monoclones from the same parent have the same VK sequence, as shown in Figure 12. The light chain sequences of monoclones belonging to the three different hybrids were diverse from each other.

[0227] Example 4: Further characterization of other Vβ17 antibodies The proliferation and activation profiles of 12 other antibodies were examined, as shown in Figure 13. These 12 additional antibodies had moderate agonistic properties and good PBMC binding and were taken forward for epitope binning and cell-based competition assays.

[0228] As shown in Figures 14A-14C, monoclones derived from one hybrid parent 23A9 were binned similarly to the positive control antibody (TCRVb17-PE).

[0229] As shown in Figures 15A-15C, monoclones derived from 23A9 and the commercial antibody were binned similarly to each other, but differently from monoclones derived from the other hybrid parents.

[0230] Example 5: Cell-based competition assay for Vβ17 antibodies Cells were treated with Live / Dead dye for 15 minutes at 4°C, followed by seeding the cells in 96-well plates. Cells were treated with different concentrations of humanized Vb17 antibody (B17B633.001) and incubated at 4°C for 40 minutes. Cells were washed and incubated with 20ug / mL purified mouse Vb17 antibody at 4°C for 40 minutes. Cells were stained with secondary antibody, washed, and read in Novocyte. As shown in Figure 16, most of the monoclones bound to cells expressing Vβ17 without competition from the commercial antibody.

[0231] [Table 8]

[0232] Those skilled in the art will appreciate that changes could be made to the embodiments described above without departing from the broad inventive concept. It is understood therefore that the invention is not limited to the particular embodiments disclosed, but is intended to cover modifications within the spirit and scope of the invention as defined herein.

Claims

1. A multispecific antibody that binds to Vβ17, (1) (i) a VH having the amino acid sequence of SEQ ID NO: 133, and including VH CDR1, VH CDR2, and VH CDR3, respectively; (ii) a VL having the amino acid sequence of SEQ ID NO: 134, and including VL CDR1, VL CDR2, and VL CDR3, respectively; (2) (i) a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 31, and including VH complementarity-determining region 1 (CDR1), VH CDR2, and VH CDR3, each having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3; (ii) a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 32, and including VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3; (3) (i) a VH having the amino acid sequence of SEQ ID NO: 65, and including VH CDR1, VH CDR2, and VH CDR3, respectively; (ii) a VL having the amino acid sequence of SEQ ID NO: 66, and including VL CDR1, VL CDR2, and VL CDR3, respectively; (4) (i) a VH having the amino acid sequence of SEQ ID NO: 99, and including VH CDR1, VH CDR2, and VH CDR3, respectively; (ii) a VL having the amino acid sequence of SEQ ID NO: 100, and including VL CDR1, VL CDR2, and VL CDR3, respectively; (5) (i) a VH having the amino acid sequence of SEQ ID NO: 167, wherein VH CDR1, VH CDR2, and VH CDR3 have the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; (ii) a VL having the amino acid sequence of SEQ ID NO: 168, wherein VL CDR1, VL CDR2, and VL CDR3 have the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively; (6) (i) a VH having the amino acid sequence of SEQ ID NO: 201, wherein VH CDR1, VH CDR2, and VH CDR3 have the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; (ii) a VL having the amino acid sequence of SEQ ID NO: 202, wherein VL CDR1, VL CDR2, and VL CDR3 have the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively; (7) (i) a VH having the amino acid sequence of SEQ ID NO: 235, wherein VH CDR1, VH CDR2, and VH CDR3 have the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; (ii) a VL having the amino acid sequence of SEQ ID NO: 236, wherein VL CDR1, VL CDR2, and VL CDR3 have the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively; (8) (i) a VH having the amino acid sequence of SEQ ID NO: 269, wherein VH CDR1, VH CDR2, and VH CDR3 have the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; (ii) a VL having the amino acid sequence of SEQ ID NO: 270, wherein VL CDR1, VL CDR2, and VL CDR3 have the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively; (9) (i) a VH having the amino acid sequence of SEQ ID NO: 303, wherein VH CDR1, VH CDR2, and VH CDR3 have the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; (ii) a VL having the amino acid sequence of SEQ ID NO: 304, wherein VL CDR1, VL CDR2, and VL CDR3 have the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively; (10) (i) a VH having the amino acid sequence of SEQ ID NO: 337, and including VH CDR1, VH CDR2, and VH CDR3, respectively; (ii) a VL having the amino acid sequence of SEQ ID NO: 338, and including VL CDR1, VL CDR2, and VL CDR3, respectively; (11) (i) a VH having the amino acid sequence of SEQ ID NO: 371, wherein VH CDR1, VH CDR2, and VH CDR3 have the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; (ii) a VL having the amino acid sequence of SEQ ID NO: 372, wherein VL CDR1, VL CDR2, and VL CDR3 have the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively; (12) (i) a VH having the amino acid sequence of SEQ ID NO: 405, wherein VH CDR1, VH CDR2, and VH CDR3 have the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively; (ii) a VL having the amino acid sequence of SEQ ID NO: 406, wherein VL CDR1, VL CDR2, and VL CDR3 have the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively; or (13) (i) a VH having the amino acid sequence of SEQ ID NO: 439, and including VH CDR1, VH CDR2, and VH CDR3, respectively; (ii) a VL having the amino acid sequence of SEQ ID NO: 440, and including VL CDR1, VL CDR2, and VL CDR3, respectively. An antibody comprising:

2. 2. The antibody of claim 1, wherein the amino acid sequences of the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 are according to the Kabat numbering system.

3. A multispecific antibody that binds to Vβ17, comprising a VH and a VL, (1) VH comprises the amino acid sequence set forth in SEQ ID NO: 133, and VL comprises the amino acid sequence set forth in SEQ ID NO: 134; (2) VH comprises the amino acid sequence set forth in SEQ ID NO: 31, and VL comprises the amino acid sequence set forth in SEQ ID NO: 32; (3) VH comprises the amino acid sequence set forth in SEQ ID NO: 65, and VL comprises the amino acid sequence set forth in SEQ ID NO: 66; (4) VH comprises the amino acid sequence set forth in SEQ ID NO: 99, and VL comprises the amino acid sequence set forth in SEQ ID NO: 100; (5) VH comprises the amino acid sequence set forth in SEQ ID NO: 167, and VL comprises the amino acid sequence set forth in SEQ ID NO: 168; (6) VH comprises the amino acid sequence set forth in SEQ ID NO: 201, and VL comprises the amino acid sequence set forth in SEQ ID NO: 202; (7) VH comprises the amino acid sequence set forth in SEQ ID NO: 235, and VL comprises the amino acid sequence set forth in SEQ ID NO: 236; (8) VH comprises the amino acid sequence set forth in SEQ ID NO: 269, and VL comprises the amino acid sequence set forth in SEQ ID NO: 270; (9) VH comprises the amino acid sequence set forth in SEQ ID NO: 303, and VL comprises the amino acid sequence set forth in SEQ ID NO: 304; (10) VH comprises the amino acid sequence set forth in SEQ ID NO: 337, and VL comprises the amino acid sequence set forth in SEQ ID NO: 338; (11) VH comprises the amino acid sequence set forth in SEQ ID NO: 371, and VL comprises the amino acid sequence set forth in SEQ ID NO: 372; (12) VH comprises the amino acid sequence set forth in SEQ ID NO: 405, and VL comprises the amino acid sequence set forth in SEQ ID NO: 406; or (13) An antibody in which VH comprises the amino acid sequence set forth in SEQ ID NO: 439 and VL comprises the amino acid sequence set forth in SEQ ID NO:

440.

4. The antibody according to any one of claims 1 to 3, wherein the antibody is a bispecific antibody.

5. The antibody according to any one of claims 1 to 3, wherein the antibody is a trispecific antibody.

6. The antibody according to any one of claims 1 to 3, wherein the antibody is a tetraspecific antibody.

7. A nucleic acid encoding the antibody of any one of claims 1 to 3.

8. A vector comprising the nucleic acid of claim 7.

9. A host cell comprising the vector of claim 8.

10. A kit comprising the antibody of any one of claims 1 to 3 and instructions for using the antibody.

11. A pharmaceutical composition comprising the antibody of any one of claims 1 to 3 and a pharmaceutically acceptable carrier.

12. A method for activating T cells that express Vβ17, comprising contacting T cells that express Vβ17 with an antibody according to any one of claims 1 to 3.

13. 10. A method for directing T cells expressing Vβ17 to a target cell, comprising contacting the target cell with an antibody of any one of claims 1 to 3, wherein a second target is present on the surface of the target cell, and wherein the contacting directs the T cells to the target cell.

14. 10. A method of inhibiting the growth or proliferation of a target cell, comprising contacting an antibody of any one of claims 1 to 3 with a target cell having a second target present on the surface of the target cell, wherein the contacting is in the presence of a T cell that expresses Vβ17, and wherein the contacting results in inhibition of the growth or proliferation of the target cell.

15. 10. A composition for use in a method for eliminating target cells in a subject, the composition comprising the antibody of any one of claims 1 to 3, the method comprising contacting the antibody with a target cell having a second target present on the surface of the target cell, the contacting being in the presence of T cells expressing Vβ17, and the contacting resulting in the elimination of the target cell.

16. 10. A composition for use in a method of treating a disease in a subject, the composition comprising an antibody according to any one of claims 1 to 3, the method comprising administering to the subject an effective amount of the antibody, the disease being caused in whole or in part by target cells having a second target present on their surface.

17. The composition of claim 16 , wherein the subject is a human.

18. The composition of claim 16, wherein the subject is a subject in need thereof.

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