Antibodies binding to constant domains of gamma delta t-cell receptors

Abstract

This invention relates to human antibodies and antigen-binding fragments thereof that specifically bind to one or more constant domains of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof. The invention also relates to novel recombinant antigens, particularly novel recombinant and / or isolated antigens comprising one or more constant domains of a gamma delta T- cell receptor (gdTCR) or a fragment or fragments thereof and antibodies that bind said antigens. Further, this invention relates to methods employing said recombinant antigens to obtain said antibodies that specifically bind to and selectively target the constant regions of a gdTCR or fragment thereof. This invention additionally relates to methods for producing and purifying said antibodies and recombinant antigens. Additionally, this invention relates to polynucleotide molecules encoding said antibodies and said recombinant antigens. It also relates to vectors containing such polynucleotides and host cells comprising such polynucleotides and methods of producing said antibodies and antigen- binding fragments. The invention also relates to methods using said antibodies, such as methods of detecting, diagnosing and treating disease using said antibodies and medicaments comprising or derived from said antibodies.

Description

[0001]ANTIBODIES AND USES THEREOF FIELD OF THE INVENTION 5 In general, this invention relates to human antibodies and antigen-binding fragments thereof that specifically bind to one or more constant domains of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof. The invention also relates to novel recombinant antigens, particularly novel recombinant and / or isolated antigens comprising one or more constant domains of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof and antibodies that bind said antigens. 10 Further, this invention relates to methods employing said recombinant antigens to obtain said antibodies that specifically bind to and selectively target the constant regions of a gdTCR or fragment thereof. This invention additionally relates to methods for producing and purifying said antibodies and recombinant antigens. Additionally, this invention relates to polynucleotide molecules encoding said antibodies and said recombinant antigens. It also relates to vectors containing such polynucleotides15 and host cells comprising such polynucleotides and methods of producing said antibodies and antigen- binding fragments. The invention also relates to methods using said antibodies, such as methods of detecting, diagnosing and treating disease using said antibodies and medicaments comprising or derived from said antibodies. 20 BACKGROUND Gamma Delta T cell and T-cell receptor Classification Human gamma (^) delta (^) T-cell Receptors (gamma delta TCRs) are heterodimeric receptors comprising a gamma chain and a delta chain. Conventionally this class of receptors is classified into 25 sub-groups (sub-classes or sub-types) dependent on variable domain usage and the associated functionality / residency of gamma delta cells expressing said receptors. For example, one common classification system involves classifying the receptors via variable chain usage which can be summarized as follows: 30 Classification of receptor via variable chain usage: Human gamma delta TCRs containing a variable delta-one chain are often termed “delta-one” or “^^” or “VD1” TCRs as they comprise gamma delta TCRs encoded in part by the TRDV1 gene and comprise TRDV1 protein sequence. Typically, delta-one TCRs are predominantly expressed on gamma delta cells found in tissues and as such, cells positive for the delta-one TCR are sometimes termed ‘tissue- resident’ gamma delta T cells. Human gamma delta TCRs containing a variable delta-two chain are often termed “delta-two” or “^^” 5 or “VD2” TCRs as they comprise gamma delta TCRs encoded in part by the TRDV2 gene and comprise TRDV2 protein sequence. Typically, delta-two TCRs are predominantly expressed on gamma delta cells found in blood and as such, cells positive for the delta-two TCR are sometimes termed ‘blood-derived’ gamma delta T cells. 10 Human gamma delta TCRs containing a variable delta-three chain are often termed “delta-three” or “^^” or “VD3” TCRs as they comprise gamma delta TCRs encoded in part by the TRDV3 gene and thus comprise TRDV3 protein sequence. Delta-three TCRs are less well-studied and can be expressed on a smaller population of gamma delta T cells. They are likely a mixture of blood and tissue-resident (see also ‘non-delta two’ classification below). 15 Additional to the above delta-one, delta-two and delta-three receptor sub-classes, there are a number of ‘other’ human gamma-delta receptors; specifically “delta-four” or “^^” or “VD4” TCRs, “delta-five” or “^^” or “VD5” TCRs, “delta-six” or “^^” or “VD6” TCRs, “delta-seven” or “^^” or “VD7” TCRs, “delta- eight” or “^^” or “VD8” TCRs. Conventionally these ‘other’ classes are not considered ‘true’ gamma- 20 delta variable domains as they are also shared with alpha-beta TCRs. Additionally, the numbers of gamma delta cells expressing gamma delta TCRs containing VD4, VD5, VD6, VD7, and VD8 are typically small. Alongside the above classification, a more simplified classification system splits all gamma delta cells 25 between one of only two categories; those cells expressing delta-two TCRs and those which do not. In this approach gamma delta cells not expressing delta-two TCRs are termed ‘non-delta two’ gamma delta cells or ‘non-haematopoietic tissue-resident’ gamma delta cells (e.g. WO2017072367A1). In essence this classification approach is in recognition of the fact that in blood, the predominant class of cells are positive for delta-two containing TCRs cells whereas ‘non-delta two’ gamma delta cells 30 predominate elsewhere (in tissues etc). Finally, another somewhat enigmatic classification system defines one populations of gamma delta cells purely by what they are not – specifically gamma delta cells which are ‘non delta-one and non delta-two’ gamma delta cells have been classified as a single group previously (e.g. see Deniger et al Clin Cancer Res. 2014 Nov 15;20(22):5708-19. doi: 10.1158 / 1078-0432.CCR-13-3451). One might assume this class of cells is therefore instead positive for TCR delta-three, delta-four, delta-five, delta- six, delta-seven, and / or delta-eight. 5 An alternate way by which gamma delta TCRs and cells expressing said receptors are classified has been through their gamma-chain usage. Whilst there are at least 14 variable gamma genes (TRGV) it is assumed that only eight of these variable genes are functional. These belong to four different structural subgroups. However, only those sub-groups for which marked functional / residency differences are noted will be discussed below. 10 Human gamma delta TCRs containing a variable-four gamma chain are termed “gamma-four” or “^^” or “VG4” TCRs as they as they comprise gamma delta TCRs encoded in part by the TRGV4 gene and comprise TRGV4 protein sequence. This sub-class of TCR is of particular interest because cells expressing atypical levels or activity of gamma-four TCR can be associated with human gut 15 inflammation. Human gamma delta TCRs containing a variable-nine gamma chain are sometimes termed “gamma- nine” or “^^” or “VG9” TCRs as they as they comprise gamma delta TCRs encoded in part by the TRGV9 gene and comprise TRGV9 protein sequence. This sub-class of TCR is of particular interest because cells 20 expressing gamma-nine TCRs often present as a heterodimeric complex with delta-two chains and as such typically predominate in blood. Finally, it must be noted that the above example classification systems are not absolute and indeed there is overlap. For example, and as already mentioned, gamma-nine TCR positive cells are often 25 delta-two TCR positive too. New classification of receptor via constant chain usage: However often overlooked is the fact that all such gamma delta TCR comprise one of two variant heterodimeric constant domains. The present inventors therefore propose an alternate approach to 30 classifying both the gamma delta TCRs themselves as well as the cells expressing such TCRs. In humans, the delta chain constant domain of a gamma delta receptor is encoded by a single human TRDC gene and as such all gamma delta TCRs contains human TRDC protein sequence – termed T-cell receptor constant protein (e.g. see Uniprot B7Z8K6; TRDC_HUMAN) (SEQ ID NO: 1). By contrast the human gamma constant chain of a gamma delta receptor is encoded by either; (i) the human TRGC1 gene and as such will contain the human TRGC1 protein - termed T-cell receptor constant protein 1 (see Uniprot P0CF51; TRGC1_HUMAN) (SEQ ID NO: 2) or; (ii) the human TRGC2 gene and as such contain the human TRGC2 protein – termed T-cell 5 receptor constant protein 2 (see Uniprot P03986; TRGC2_HUMAN) (SEQ ID NO: 3) Hence rather than classifying all gamma delta T cell sub-types by variable domain usage, one could instead consider classifying such receptors by constant domain usage. In doing so it is thus possible to divide all gamma delta cells into one of only 2 alternate sub-types as follows. 10 Human “GC1” receptors and cells expressing GC1 receptors This gamma delta TCR sub-class comprises TCRs containing the TRDC and TRGC1 constant domains. Hence it is proposed herein that TCRs of this sub-class are termed “GC1” TCRs. As such gamma delta cells expressing this sub-class of TCR can thus be abbreviated to “GC1” positive gamma delta cells. 15 Human “GC2” receptors and cells expressing GC2 receptors This gamma delta TCR sub-class comprises TCRs containing the TRDC and TRGC2 constant domains. Hence it is proposed herein that TCRs of this sub-class are termed “GC2” TCRs and as such gamma delta cells expressing this sub-class of TCR can thus be abbreviated to “GC2” positive gamma delta 20 cells. Whilst defining such cells in this manner is thus a novel possibility, without antibody tools able to distinguish these two sub-groups clearly and reliably it is little more than a theoretical academic exercise in most circumstances. Hence there is a need for better, more selective antibodies and to 25 develop such, there is first a need for better antigens to discover and characterise such antibodies. A sub-set of such antibodies may also be considered suitable as a novel class of therapeutic medicaments. One notable challenge in the provision of antigen tools to aid with discovery of antibodies capable of 30 selectively recognizing and binding GC1 and / or GC2 TCRs are the respective TRGC1 and TRGC2 constant domains. Whilst both human TRGC1 and TRGC2 domains share >90% amino acid sequence homology, they differ in marked and unique ways not observed in constant domains of conventional alpha beta TCRs. Specifically, whilst gamma delta GC1 TCRs comprising TRDC / TRGC1 heterodimers contain a canonical single interchain disulfide linkage, the GC2 TCRs comprise TRDC / TRGC2 heterodimers contains no such interchain disulfide linkage. This is unique amongst human T-cell Receptors and is because the TRGC2 gene segment contains no partner cysteine to pair with the cysteine present on cognate TRDC domains. Instead for the TRGC2 domain, this cysteine is replaced by a bulky hydrophobic tryptophan (Trp133, SEQ ID NO: 12) as shown in Figure 4. Alongside this 5 atypical ‘missing’ interchain linkage, the TRGC2 constant domain is also larger, exhibits multiply sized isoforms, and exhibits differing N-linked glycosylation patterning. The resulting differences in GC1 and GC2 TCR architectures makes the design and provision of authentic and representative antigens of this invention more challenging. 10 To summarize further, a comparison of the GC1 and GC2 TCRs is presented below in Table 1. TABLE 1 TCR Feature GC1 TCRs GC2 TCRs Overall Size Smaller relative to GC2 Multiple allelic variants, all larger than GC1 TRGC ‘Connecting’ Smaller relative to TRGC2 Larger relative to TRGC1 and due to at Region least one additional insert (or multiple inserts dependent on the allele) TRGC cysteine Yes, TRGC1 (Cys121; Uniprot No, cysteine replaced with a bulky employed in numbering of TRGC1_Human aromatic acid (Trp137; Uniprot interchain pairing P0CF51 (SEQ ID NO: 2; also see numbering of TRGC2_Human P03986 Cys117 SEQ ID NO:11) SEQ ID NO: 3, also see Trp133 SEQ ID 12) TRDC cysteine 110 is Yes No, instead it appears ‘orphaned’ paired Inter-chain disulfide Yes No bond formed between TRDC and TRGC heterodimer Potential TRDC 2 sites (N14 and N77 TRDC SEQ 2 Sites (N14 and N77 TRDC SEQ ID glycosylation sites ID NO: 1) NO: 1) Potential TRGC N- Four sites (N66, N120, N126, Five Sites (N66, N120, N136, N142, linked Glycosylation N135 Uniprot numbering of N151, Uniprot numbering of Sites (and positions) TRGC1_Human P0CF51 SEQ ID TRGC2_Human P03986 SEQ ID NO: 3) NO: 2) Therapeutic Human Monoclonal antibodies selective for specific Gamma Delta TCRs. To date, a number of discovery projects have been undertaken primarily to identify and isolate human or humanized therapeutic antibodies capable of binding and / or modulating and / or depleting and / or 5 activating cells expressing gamma delta TCRs. Typically, such discovery projects have focused on the discovery and use of antibodies as medicaments to selectively activate specific sub-sets of gamma delta cells such to ameliorate signs and symptoms of diseases including cancers and infections. Example of such projects are summarized in Table 2 below. 10 TABLE 2 Sub-Class of Example Project Possible use ? Possible Advantages ? gamma delta TCR targeted by antibody-based moieties Gamma nine WO2015156673 and de Medical treatment for the Targeting and Bruin et al 2018 treatment of cancer or an activation of gamma- Oncoimmunology; 7(1): infectious disease nine TCR positive cells e1375641 doi: predominantly found 10.1080 / 2162402X.2017.137 in blood 5641 Gamma four WO2021171002 Pharmaceutical Targeting and composition for the activation of gamma treatment of disease four TCR positive cells often displaying markers of gut tissue residency Delta one WO2021032960 Pharmaceutical Targeting and composition for the activation of ‘tissue- treatment of disease resident’ delta-one TCR positive cells Delta one WO2019147735 Medicament for use in Inhibiting the treating diseases activation of gamma delta T cells Delta two WO2015156673 and de Medical treatment for the Targeting and Bruin et al 2018 treatment of cancer or an activation of delta-two Oncoimmunology; 7(1): infectious disease TCR positive cells in e1375641 doi: blood 10.1080 / 2162402X.2017.137 5641 Delta three WO 2019099744 For creating Ex-vivo enrichment of pharmaceutical delta-three TCR composition comprising positive subset delta-three enriched gamma delta cells for the treatment of conditions including cancer and infectious diseases The use of antibodies as medicaments to modulate specific gamma delta T cells As outlined in Table 2, various strategies have been undertaken to date focused on the discovery of antibodies which selectively bind to, target, and / or modulate (typically through activation) certain sub- 5 sets of gamma delta T cells. Associated with such strategies, those skilled-in-the-art have typically outlined that the sub-set of gamma delta T cells they are activating is likely the most preferred sub- type. For example, it has been suggested that antibodies which selectively target and activate delta- two TCR positive cells are most desirable because (i) delta-two positive cells comprise 90-95% of peripheral blood gamma delta T cells; (ii) they consistently generate a pro-inflammatory cytotoxic T 10 cell population; (iii) they are able to present antigen and (iv) they are associated with good prognosis in cancer patients. In contrast, it is suggested that targeting the other major sub-set of gamma delta cells - namely the delta-one cell sub-set – is less desirable given (i) delta-one cells are infrequently present in blood and (ii) delta-one cells exhibit more variable prognosis profiles. However, other artisans suggest the converse - specifically that delta-one cells are a more preferred sub-set to activate and to use in the treatment of cancer. For example, some authors suggest that delta-one cells may be preferred whereas delta-two cells are (i) dysfunctional in some cancer patients 5 and (ii) susceptible to activation induced anergy and exhaustion. Finally, some investigators suggest that gamma delta cells are in fact undesirable and should be depleted rather than selectively activated during cancer treatment regimens. Indeed, these researchers – some associated with Nybo Therapeutics Inc (Boston, MA, USA) - consider killing or 10 depleting gamma delta cells, particularly delta-one TCR positive cells, as the best option and propose the use of selective antibodies to mediate dependent cellular cytotoxicity (ADCC) based depletion of gamma delta cells accordingly. This is because these investigators consider gamma delta cells, and more specifically delta-one TCR positive gamma delta cells, to be immunosuppressive, particularly in pancreatic cancer. 15 Alongside example antibody clinical trials as outlined above in Table 2, to date there have also been a significant number of example cell therapy products wherein delta two or delta one enriched populations of cells have been used as cell therapy medicaments. Such cell therapies typically comprise hundreds of millions of gamma delta cells per dose. Such medicines are highly complex, costly to 20 develop, store, distributed and administer – particularly to large numbers of patients. Hence there is a need for ways and means to increase the number of gamma delta cells in a patient in need of treatment without the need for such complex cell therapies. In summary, during the pursuit of antibody-based medicaments and cell therapies designed to harness 25 gamma delta T cells, numerous alternative strategies have been explored and described at length to date. The need for “pan-gd” medicines Whilst it is possible that all such approaches for the use of antibodies as medicaments to modulate 30 specific gamma delta T cells have merit, there is clearly a need to better understand and characterize this class of medicaments. Many approaches to date are narrow in focus which may result in less effective antibody medicaments. In many circumstances a selective, partisan choice of one sub-type of gamma delta cells to target is not always optimal since it ignores potential holistic benefits of activating multiple sub-classes of gamma delta cells. There is therefore a need for antibodies that are capable of recognising and binding specifically and selectively to multiple sub-classes of gamma delta TCR via one or more constant domains of a gdTCR (termed a “pan gamma delta” or “pan gd” antibody). Such antibodies are not restricted to binding only one sub-class of gamma delta TCR (for example a delta-one TCR) but can bind to multiple sub-classes of gamma delta TCR (for example delta-one, delta- 5 two and delta-three TCRs). For instance, researchers focused on the discovery of antibody-based medicaments selective for delta- one gamma delta cells with a more tissue-resident distribution may then consider use of such medicaments to ameliorate the signs and symptoms of tissue-derived cancers – so called solid tumors. 10 However, such antibody-based medicaments may prove sub-optimal for this purpose as they do not also target delta-three cells also reportedly present in tissues – and sometimes in greater numbers. Therefore antibody-based medicaments capable of activating both classes could be used to underpin more holistic treatment regimens wherein both blood and tissue resident gamma delta cells are activated resulting in a more systemic surveillance of both blood and tissue. 15 As another example, other investigators with a preference for developing antibodies specifically designed to activate blood-centric gamma-nine gamma delta cells may then focus on their use in the treatment of leukaemia or so called ‘liquid’ tumors of the blood and where delta-two gamma delta cells predominate. However primary liquid tumors of the blood can develop via metastasis to become 20 secondary tissue / solid tumors where gamma-nine gamma delta cells are less prevalent. In this instance, and once again, an ideal antibody-based medicaments might be one that is not only capable of selectively activating blood-centric gamma nine cells but also tissue-resident delta-one cells. Once again, treatment of cancer with such medicaments may better ensure a more holistic, systemic activation of gamma delta cells and enhanced, systemic tumor surveillance. 25 The same point can also be made when considering antibodies designed to selectively activate gut resident gamma-four TCR positive gd-cells. For example, primary tumors of the gut metastasize to other tissues often via the blood and lymphatic system. Hence once again an ideal antibody-based medicament is one capable of activating more than just gut-resident, gamma-four TCR positive gamma 30 delta cells. To discover and fully characterise such antibody-based medicaments capable of selectively target multiple sub-classes of gd cells and induce proliferation in all sub-classes of gamma delta T cells – be they the delta one, delta two or delta three sub-class, a novel suite of antigens is needed. Provided herein are such a novel antigen tool set so designed to aid discovery of the new class of antibodies and antibody-based medicaments also provided herein. 5 These antibodies and antibody-based medicaments exhibit desirable characteristics and technical effects which enable better treatment of patients. Through the recognition of antigens common to multiple classes of gamma delta T cells these antibodies and antibody-based medicaments exhibit features which can be leveraged to aid with more effective dosing regimens, more real-time patient monitoring, patient response and responsiveness rates, alongside improved patient stratification 10 regimens. These antibodies can also be employed as superior tools to better understand the biology and character of gamma delta T cells and sub-classes thereof. The novel approaches, methods, and treatment regimens thereby conceptualized by the availability and characterization of these novel antibodies are also provided herein. 15 Anti-gamma delta TCR antibody based medicaments; measuring target engagement and accurately characterizing conferred effects. As outlined above, a variety of differing antibody-based medicaments targeting gamma delta TCRs have been prioritized and progressed to the clinic. To the best of our knowledge all such medicaments in clinical development to date selectively bind and target a variable domain as summarized above. 20 However, one seemingly overlooked consideration in developing such medicaments is the need to optimally characterize and measure gamma delta TCR target engagement and conferred functional effects. There is a need for better medicines and better methods to monitor gamma delta TCR engagement, in particular when targeting tissue resident gamma delta cells. 25 This need is particularly pressing in human and primate studies as this group of mammals are defined as ‘gamma delta low’ species (<5% of lymphocytes in blood). In contrast, certain other mammals such as ruminants are sometimes termed ‘gamma delta high’ species given significantly higher numbers (15%-60%) observed in immune compartments. 30 Consequently, whilst these cells are often considered fundamentally important for immune surveillance and catalysis, they form a very small number of immune cells in human blood. Furthermore, within the blood, the numbers of delta one positive and delta three positive gamma delta are even lower given their tissue preference / residency. Hence developing medicines which may target and activate delta one and delta three cells may be desirable but the very small numbers of delta one and delta three cells in blood make clinical development and patient triaging more challenging. In such situations perhaps the only alternative option is to measure effects via complex tissue biopsy which is highly invasive. 5 For further example and as described above, certain medicaments are known which selectively target and modulate gamma delta cells expressing TRDV1 (delta one, VD1) containing TCRs. This class of gamma delta cells are often found in tissues and solid tumors. When developing such antibodies as medicines one essential requirement during clinical development is the ability to characterize and model target receptor engagement, occupancy and conferred technical effects. The industry-wide 10 challenges in this space are manyfold but these challenges are further amplified given the predominant tissue-resident nature of delta one TCR expressing cells. For example, measuring target engagement and conferred effects of predominantly tissue resident immune cells is difficult without invasive, error prone, and time-consuming tissue biopsy. This is further confounded by the requirement to ship the resected and often labile biopsied tissue samples to specialized laboratories 15 for further processing. Additionally, given the anticipated rapid effects of antibody target engagement - such as TCR downregulation - one may be unable to accurately measure target engagement in such tissue biopsies as the target cells become ‘invisible’. As a consequence, it may be very difficult to determine optimal dosing regimens, patient response rates and treatment regimens, or characterize cause-and-effect mechanisms of action of such medicaments. 20 In sum, developing effective patient regimens with antibody medicaments which engage tissue prominent or resident delta one or delta three gamma delta TCR positive cells in ‘gamma delta low’ environment is very difficult given the smaller numbers of cells for analysis in the blood. Consequently, leveraging most desired and most robust ‘liquid biopsy’ strategies to aid guide treatment regimens 25 may not be possible. Further, given TCR downregulation will further hamper an ability to detect target engagement of already small population better medicines are needed which are able to engage tissue resident cells alongside more prominent blood cells more readily measured and monitored. The antigens as provided herein have been designed to aid in the discovery of new antibodies and 30 antibody-based medicaments capable of binding to domains present on both blood and tissue resident cells. In turn such provisions have conceptualized and enabled more effective methods of treatment informed by the ability of such medicines to engage tissue resident targets whilst in parallel monitoring effects in the surrogate blood compartment. This allows for near real-time analysis of prevailing gamma delta two positive cells in the blood which can operate as a target engagement and response- rate surrogate for more difficult to access tissue resident gamma delta cells. 5 SUMMARY OF THE INVENTION The present invention provides human antibodies and antigen-binding fragments thereof that specifically (and selectively) bind to one or more constant domains of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof. The invention also relates to recombinant and / or isolated 10 antigens comprising or consisting of one or more constant domains of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof. Therefore, the present invention provides antibodies that selectively bind to the recombinant antigens defined herein. The constant domain may be TRDC or a fragment thereof and / or TRGC1 or a fragment thereof and / or TRGC2 or a fragment thereof. 15 According to a first aspect of the invention, human antibodies or antigen-binding fragments thereof are provided which specifically bind to human TRGC2 / TRDC heterodimeric constant domain antigen. In some embodiments, the antibody or antigen-binding fragment thereof does not bind to a variable domain of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof. Said antibodies may also specifically bind to recombinant antigens comprising one or more constant domains of a 20 gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof. In some embodiments, the antibodies or antigen-binding fragments thereof also specifically bind human TRGC1 / TRDC heterodimeric constant domain antigen. 25 In some embodiments, the antibodies or antigen-binding fragments thereof specifically bind the constant domain TRDC or a fragment thereof, optionally human TRDC or a fragment thereof. In some embodiments, the antibodies or antigen-binding fragments thereof specifically bind the constant domain TRGC1 or a fragment thereof, optionally human TRGC1 or a fragment thereof. 30 In some embodiments, the antibodies or antigen-binding fragments thereof specifically bind the constant domain TRGC2 or a fragment thereof, optionally human TRGC2 or a fragment thereof. In some embodiments, the antibodies or antigen-binding fragments thereof selectively bind the constant domain TRDC or a fragment thereof and / or TRGC1 or a fragment thereof and / or TRGC2 or a fragment thereof, optionally wherein the constant domain(s) are human. 5 In some embodiments, the antibodies or antigen-binding fragments thereof selectively bind the constant domain TRGC1 or a fragment thereof and the constant domain TRGC2 or a fragment thereof, optionally wherein the constant domain(s) are human. According to one aspect of the invention, there is provided an anti-constant gdTCR antibody or antigen- 10 binding fragment thereof as defined by SEQ ID NO herein, for example those presented in Table 3. Also provided herein are methods of using said antibodies, including methods of treating a disease or disorder in a subject, comprising administering to the subject the antibody or antigen-binding fragment thereof provided herein, optionally wherein the disease is cancer. 15 Also provided herein are recombinant antigens used to identify and develop antibodies of the invention. In one aspect the recombinant antigens may be monomeric and comprise or consist of, in a N-terminal 20 to C-terminal direction: a. optionally a leader sequence; b. one or more constant domains of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof; and c. a dimerization domain. 25 In another aspect the recombinant antigens may be dimeric and comprise or consist of a first sub-unit and a second sub-unit, wherein the first sub-unit comprises or consists of, in a N-terminal to C-terminal direction: a. optionally a leader sequence; 30 b. one or more constant domains of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof; and c. a dimerization domain; and the second sub-unit comprises or consists of, in a N-terminal to C-terminal direction: a. optionally a leader sequence; b. one or more constant domains of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof; and c. a dimerization domain. 5 In some embodiments the recombinant antigen is homodimeric. In some embodiments the recombinant antigen is heterodimeric. Also provided herein are nucleic acids that encode a recombinant antigen as described herein. Also provided herein are nucleic acids that encode an antibody as described herein. Also disclosed are 10 vectors comprising the nucleic acid as described herein. Also disclosed are host cells comprising the vector as described herein. Also provided herein is a method of producing an antibody or antigen binding fragment as defined herein, comprising culturing a vector as defined herein or a host cell as defined herein under conditions 15 allowing expression of the antibody or fragment and recovering the antibody or fragment. Also provided herein are antigen libraries comprising two or more recombinant antigens described herein. 20 Also provided herein is the use an antigen as described herein in a method of obtaining an antibody. Also provided herein are antibodies obtained or obtainable via a method as described herein. In one aspect there is provided a method of obtaining antibodies that specifically bind to the constant regions of a gdTCR or fragment thereof, the method comprising using at least two of the recombinant 25 antigens as described herein. In one aspect there is provided a method of obtaining antibodies that specifically bind to the constant regions of a gdTCR or fragment thereof, the method comprising: a. providing an antibody display library; 30 b. employing sequential affinity screening of the antibody display library using at least two of the recombinant antigens as described herein in any aspect or embodiment to identify candidate clones that specifically bind to the TRDC and / or TRGC regions of a gdTCR; c. obtaining antibodies specific to the TRDC and / or TRGC regions of a gdTCR. Also provided herein is the use of an antigen as described herein in a method of screening an antibody library. Also provided herein is an isolated recombinant peptide comprising or consisting of the amino acid 5 sequence of any one of SEQ ID NO: 33 to 50. Also provided herein is the use of an antigen as described herein in a method of immunizing an animal. Also provided herein is a method of making an antigen as described herein. 10 Also provided herein are antibodies which selectively and specifically bind to one or more of the antigens described herein. One primary goal of the antigens provided herein is the creation of a library of antigens suitable as 15 aids to help identify antibodies which selectively bind to GC1 and / or GC2 sub-classes of gamma delta TCR, or both. Such antibodies, and the antigens used to identify them, form part of the invention. Additionally conceived of, and provided herein, is a library of novel tool antibodies to aid identification and characterisation of a novel class of immune cells, to use as medicaments, to inform patient 20 treatment regimens or responsiveness, and to characterize sub-sets of gamma delta T cells which up until now have not been characterizable and poorly defined. BRIEF DESCRIPTION OF THE DRAWINGS 25 Figure 1: Constant Domain Guidance. (1A) Schematic summary of the gamma delta TCR and areas of notable variation. i = The variable domain (preferably not included in antigen); ii = The “constant” domain – also variable; variation conferred by TRGC gene usage; Exon 2 multiplication; Disulfide linkage; N-linked glycosylation profile (up to 20Kd);Final size / charge; iii =TRGC exon 2 encoded domain of various sizes due to insert multiplication; iv = The hyper variable CDR3 V(D)J domain (average length 30 increases with human age). The two greyed boxes indicate the structural domains of particular interest to this invention. The greyed boxes each comprise (canonical) beta-stranded IgG-like sub-unit of the gamma and delta constant domain respectively. These isolated sub-units are C-terminal of the hypervariable VDJ region and continue through to less structured regions. These greyed areas are of particular interest for inclusion into antigens as described herein. (1B) Example Full Length Human Protein Sequence for TRDC, TRGC1 and TRGC2 proteins domains. Example human, cynomolgus and murine protein sequence shown for: Human TRDC sequence (B7Z8K6 TRDC_HUMAN uniprot.org also termed IMGT.org allele TRDC*01); Human TRGC1 5 sequence (P0CF51 TRGC1_HUMAN uniport.org also termed IMGT allele TRGC1*01); Human TRGC2 sequence (P03986 TRGC2_HUMAN uniport.org also termed IMGT allele TRGC2*06); Human TRGC2 sequence (alternate allele, GenBank: AAB63312.1); Cynomolgus TRDC (A0A7N9CA91_MACFA uniport.org); Cynomolgus TRGC (G7P2C2_MACFA uniport.org); murine TRDC (A0A0G2JEU3_MOUSE) uniprot.org; murine TRGC1 (A0A075B5Z0_MOUSE); murine TRGC2 (A0A075B5Z2_MOUSE) 10 Figure 2: Cartoon adaption of a crystal structure of an example TCR of the “GC1” gamma delta TCR class. Cartoon of 1HXM gamma delta TCR crystal structure. This an example of a delta two, gamma nine TCR inclusive of constant domain and variable domain. Note cartoon does not depict a full length TCR as the components of regions encoded by TRDC and TRGC (C-terminal unstructured or connecting 15 region, the transmembrane domain, and cytoplasmic tail / stump) are not incorporated. Such TCRs are typically expressed on gamma delta cells predominant in blood and conventionally termed “delta two” TCRs. By the classification system as now proposed herein, this TCR is an example of a “GC1” class of TCR because the constant domain employed is the TRDC / TRGC1 variant. Location of the canonical beta strands found in the Ig-like constant TRGC1 and TRDC domains are indicated by brackets. Cartoon 20 sourced from https: / / www.rcsb.org / 3d-view / 1HXM. Figure 3: TRGC and TRDC domain structure and sequence including example antigen numbering scheme and key residues (3A) TRGC and TRDC domains in isolation and inclusive of unstructured regions, alpha helical transmembrane regions, and cytoplasmic tail / stumps. Cartoon structure 25 prediction of (i) TRDC, (ii) TRGC1 and (iii) TRGC2 domains in isolation and inclusive of the beta strands of the Ig-like domain (boxed), unstructured connecting regions, helical transmembrane domain and cytoplasmic stump. No N-terminal variable domains are shown. Cartoons adapted from AlphaFold (alphafold.com) - for TRDC see AlphaFold AF-B7Z8K6-F1; for TRGC1 see AF-P0CF51-F1; for TRGC2 see AF-P03986-F1. Cartoons adapted from screenshots and for illustrative purposes only (and not 30 necessarily to the same scale) (3B) TRDC domain structure. The full length TRDC sequence (SEQ ID NO: 1) is shown (amino acids 1-153) alongside an associated AlphaFold model (see also 3A). Highlighted (bold) is the area of particular interest when designing antigens as described herein (Ser1 to Cys110). Contained within this region is the B-strand structured sequence between and inclusive of residues Ser8 and His81. Beta strands (predicted by Uniprot KB) at position 8-14, 17-24, 26-28, 31-35, 37-42, 35 46-49, 53-63, 70-75 and 78-81 are underlined.-(3C) TRGC1 domain structure. The full length TRGC1 sequence (SEQ ID NO:2) is shown (amino acids 1-173) alongside an associated AlphaFold model (see also 3A). Highlighted (bold) is the area of particular interest when designing antigens as described herein (Asp5 to Cys121). Contained withing this region is the B-strand structured sequence between and inclusive of residues Lys11 through to Phe105. Beta strands (predicted by Uniprot KB) at positions 5 11-15, 19-25, 26-40, 43-48, 49-51,63-65,68-78, 79-81, 82-84, 86-91, 101-105 are underlined. (3D) TRGC2 domain structure. The full length TRGC2 sequence (SEQ ID NO: 3) is shown (amino acids Asp1 to Ser190) alongside an associated AlphaFold model (see also 3A). Highlighted (bold) is the area of particular interest when designing antigens as described herein (Asp5 to Phe105). Contained within this region is the B-strand structured sequence between and inclusive of residues Lys11 through to 10 Phe105. Beta strands (predicted by UniProtKB, plus an additional as modelled by alphafold for 11-15) at positions 11-15, 24-26, 28-39, 42-51, 66-77, 89-92 and 101-105 are underlined. Further detail of TRDC, TRGC1 and TRGC2 domain structure / sequence respectively. (3E) The beta strand intervening loops of TRDC1, TRGC1 and TRGC2 (bold, underlined). 15 Figure 4: Protein sequence alignment of human TRDC and TRGC domains. Alignment of different TRGC1 and TRGC2 constant domain sequences (BLOSUM 62 scoring matrix). Consensus sequence shaded. Two variant TRGC2 alleles are shown to highlight single or double inserts for one example alternative TRGC2 allele. Only a TRGC1 single insert and TRGC2 double insert allele examples are shown herein. However reportedly additional multiplications have been observed in certain other 20 TRGC2 variants (see Buresi et al,.1989;29(3):161-72. doi: 10.1007 / BF00373641. Position of the Cys of TRDG1 which pairs with cys contained in the TRDC domain is indicated by box. Also highlighted in the same box is the TRGC2 trp at this position – no interchain cysteine is unique amongst all human TCR constant domains. 25 Figure 5: Example antigen sequence inclusive of an example downstream junction (5A) Schematic cartoon of an example heterodimeric (left) and homodimeric (middle and right) antigens. Optionally, heterodimerisation can be encouraged with aid of knob-in-hole Fc domains. (5B) Example heterodimeric sequence guide. Example junction shown between antigen and associated purification / dimerization domain. In this example, the underlined sequence comprises IgG-like 30 domain of the TRDC and TRGC1 constant domains incorporated into the antigen. Note the dual identity of cysteine at the junction of the gamma delta constant domain and the Ig Fc domain. This Cys can be numbered either as the first cysteine of the Fc sequence (220 / 233; Eu or Kabat numbering respectively) or equally as cysteine 110 of TRDC (SEQ ID NO:1) and cysteine 121 (SEQ ID NO:2) of TRGC1 respectively. When present these cysteines can form an interchain disulfide bridge in antigens as provided herein. Full length IGHG1 sequence not shown. Figure 6: Example library of TRGC1 / TRDC heterodimeric human (SEQ ID No: 33 & 34), cyno (SEQ ID 5 No: 35 & 36) and murine (SEQ ID No: 37 & 38) antigens. Note for each antigen sub-unit, a cleavable leader (SEQ ID No: 21) can be included at the N-terminus to encourage secretion in mammalian cells such as CHO and HEK293. Also note each sub-unit contains a C-terminal knob or hole Fc domain (SEQ 24 or 25 respectively) to encourage heterodimerization. 10 Figure 7: Example library of TRGC2 / TRDC heterodimeric human antigens. The first antigen (SEQ ID No: 39 & 34) comprises human TRGC2 and TRDC authentic or wild-type sequence and as such no interchain disulfide bond can form between TRGC2 and TRDC chains - the TRDC Cys110 cannot form a disulfide bridge with TRGC2 partner chain which naturally lack a cysteine at the orthologous position. Hence in this antigen, the TRDC Cys110 is present but principally unpartnered. The second antigen 15 (SEQ ID No:40 & 34) comprises TRGC2 sequence with a Trp137Cys change such to allow the TRGC2 chain to form a disulfide bond between TRGC2137Cys and TRDC Cys110. The third antigen (SEQ ID No: 39 & 41) comprises wild-type TRGC2 sequence (Trp137, no cysteine) and TRDC sequence with Cys110Ser modification such to ensure there is no unpartnered Cys in the TRDC sub-unit. Note for each antigen sub-unit, a cleavable leader (SEQ ID No: 21) can be included at the N-terminus to encourage 20 secretion in mammalian cells such as CHO and HEK293. Also note each sub-unit contains a C-terminal knob or hole Fc domain (in this example SEQ 24 or 25 respectively) to encourage heterodimerization. Figure 8: Example library of TRDC, TRGC1 and TRGC2 homodimeric human antigens. Note these are homodimers antigens comprising two identical sub-unit with wild-type Fc fusion domains at their C- 25 termini. Also note for each antigen sub-unit, a cleavable leader (SEQ ID No: 21) can be included at the N-terminus to encourage secretion in mammalian cells such as CHO and HEK293. Figure 9: Example library of human heterodimeric antigens comprising both constant domain sequence AND variable domain sequence of Table 7. For Antigen CytAnt10 (SEQ ID No:45 and 46), 30 the 1HXM variable domain (and CDR3) sequences are employed. For Antigen CytAnt11 (SEQ ID No:47 and 48), the 6G7D variable (and CDR3) sequences are employed. For Antigen CytAnt12 (SEQ ID No:49 and 50), the 7LLI variable (and CDR3) sequences are employed. Note for each antigen sub-unit, a cleavable leader (SEQ ID No: 21) can be included at the N-terminus to encourage secretion in mammalian cells such as CHO and HEK293. Also note each sub-unit contains a C-terminal knob or hole 35 Fc domain (SEQ 24 or 25 respectively) to encourage heterodimerization. Figure 10: Reduced and Non-reduced analysis of antigens described herein. Example non-reduced and reduced (suffixed as ‘r’) SDS-PAGE analysis of purified gamma delta constant domain antigens against M Protein Standard Marker (Bio-Rad Laboratories Ltd, Hertfordshire UK. A) Example analysis 5 of purified heterodimeric antigens; Lane order: 1= CytAnt01, 2 = CytAnt02, 3= CytAnt03, 4 = CytAnt04, 5 = CytAnt05,6 = CytAnt06, 10 = CytAnt10, 11 = CytAnt11, 12 = CytAnt12 B) Example analysis purified homodimeric antigens Lane Order 7 = CytAnt7, 8 = CytAnt8, 9= CytAnt9. Figure 11: Example stepwise library screening cascade using the TRDC / TRGC antigens. Initial 10 antibody library sequences can be derived from either a naive or immunized source to generate the initial repertoire of antibodies (or fragments thereof such as scFV and Fab based sequences). Screening can be undertaken in parallel or in series as shown here. For further detail of strategies employed herein (A, B, C and D) – see Figure 12. 15 Figure 12: A summary of four different antigen / library discovery strategies. The strategies presented herein used human scFV phage display libraries N05, N06, S01, S02 to discover the human anti-TRDC and anti-TRGC antibodies provided herein. Strategy A, B, C and D are presented in Figure 12 A, B, C and D respectively. See Table 6 for further information on the antigens described herein. (A): Focus on anti- TRDC selective antibodies. (B): Focus on TRGC1 and TRGC2 selective antibodies. (C): Focus on TRGC1 20 and TRGC2 selective antibodies (alternate approach to (B)). (D): Focus on TRGC2 selective antibodies. Figure 13: A summary of master-plated scFV phage outputs in the “primary screen” ELISA assays against the antigens as indicated. Also indicated is the library and screening strategy employed to generate said outputs. 25 Figure 14: A summary of the cross-reactivity of the 29 clones in the second screen ELISA assays against the antigens as indicated. (A): Results presented for 29 clones in a tabulated form. Also indicated is the library and screening strategy employed to generate said clones. For these secondary- screen ELISA assays, the antigens were either plate-captured as biotinylated antigen (prefixed “Bio-”)30 with neutravidin or not biotinylated and plate-captured. The ELISA values are recorded and also grey- scaled heat maps created. Of note only clone 697 exhibited significant signal to background human IgG (last column). (B) Results for a subset of example clones exhibiting different target antigen selectivity profiles presented in bar chart format. Examples include an antibody specific for TRGC2 containing antigens, an antibody which is specific for TRGC1 containing antigens, and an antibody cross reactive to both antigens – antibodies 1, 2 and 3 respectively. Figure 15: Example analysis of fresh blood (PBMC purified) highlighting the relative abundance of 5 the three different subsets of gamma delta cells. The top three plots indicate a standard step-wise flow gating method from left to right comprising gating on forward / side scatter (to avoid debris) then singlets, then live cells. The lower three plots show subsequent analysis on CD3xVD1, CD3xVD2 and CD3xVD3. For this donor (arbitrarily selected) the delta two gamma delta cell content (middle lower plot) is clearly visible at approximately 2% of total CD3 positive immune cells, whilst the lower left plot 10 (delta one) and the lower right plot (delta three) are less visible (both at less than 1% total CD3 positive cells). This aligns with the consensus view which often terms delta-two positive cells as ‘blood resident’ whilst delta-one and delta-three cells as more tissue-resident. Figure 16: Example use of an antibody which selectively binds gamma delta one, delta two and delta 15 three positive cells to increase the relative numbers of all three populations in blood PBMCs. Tabulated results on day zero (left hand table pre-incubation with antibody) and day 16 (right hand table) are shown. Significant increases as a proportion of total CD3+ cells is recorded. Plots below tables provide a visual guidance of the delta one (VD1), delta two (VD2) and delta three (VD3) gating strategy and results. This gating was preceded by stepwise, forward / side, then singlet, then live, then 20 CD3+ gating (also see Figure 15 for this pre-gating). Figure 17: Antibody which selectively binds gamma delta one, delta two and delta three positive cells induced down-regulation of gamma delta TCR with antibodies. All three sub-classes (delta one, delta two and delta TCR positive gamma delta cells) exhibited a titratable TCR downregulation upon 25 engagement with the two different antibody clones which recognize and bind all three sub-types. Figure 18: Summary of antibody sequences inclusive of Clone ID, domain, chain, and SEQ ID categorization 30 Figure 19: Cancer cell killing. Primary human PBMCs enriched for gamma delta cells were mixed with a human cancer cell line. Antibody clones were then titrated into the mix. OKT3 (anti-CD3) was used as a positive control. X / Y axis plots shown report antibody concentration versus antibody induced cell killing (as measured by increased bioluminescence). Absolute values shown on left-hand graph, relative values versus base-line shown on right-hand graph. Figure 20: Anti gamma-delta TCR constant domain antibody binding to gamma delta T-cells. X / Y plots of anti-constant domain antibody % binding to gated population vs titrated antibody concentration. Binding profile to alpha-beta negative gated, gamma delta enriched PBMCs (top plot, boxed). Binding 5 profile to delta-one gated population (bottom left plot). Binding profile to delta-two gated populations (bottom middle plot). Binding profile to delta-three gated populations (bottom right plot). Figure 21: Anti gamma-delta TCR constant domain antibody induction of delta T-cells proliferation. Bar chart summary of fold-change in gamma delta T-cell number overtime (mean; 2 donors) for 10 exemplar anti-constant domain antibodies (labelled as CYT Ab1 and CYT Ab2) versus sub-type specific Comparators as indicated. Fold change in delta-one positive gamma delta T-cells (left hand bar chart), in delta-two positive cells (middle bar chart), in delta-three positive cells (right bar chart). Figure 22: Anti gamma-delta TCR constant domain antibody induction of delta T-cells degranulation. 15 X / Y plot measuring gamma delta T-cell CD107a levels vs titrated antibody concentration for two exemplar anti-constant IgG1 antibodies (CYT Ab1 or CYT Ab2) as described herein or non-binding negative control IgG1 (as indicated). Analysis of delta-one gate (left hand plot), delta-two gate (middle plot) ad delta-three gate (right hand plot). 20 Figure 23: Anti gamma-delta TCR constant domain antibody induced gamma delta T-cell killing of tumour cells. (A) Composition of gamma delta enriched PBMCs used in the co-incubation cytotoxicity study (B) X / Y plots of the results of the gamma delta cell / cancer cell co-incubation; % live tumour cells vs titrated antibody test article (as indicated) after co-incubation. Left-hand plot highlights anti- constant domain antibody mediated effects for two exemplar antibodies as described and discovered 25 herein (CYT Ab1 and CYT Ab2) versus a non-binding control IgG1. Right-hand plant compares the relative potency of these anti-constant domain antibodies to comparator sub-set specific antibodies as indicated.Figure 24: Same assay comparisons with differing anti-constant domain antibodies (A) Binding to 30 PEER cells. Studies highlight that the TRGC1 / TRDC selective A10 anti-constant domain antibody does not bind PEER cells effectively (B) Binding to primary gamma delta T-cells gated on VD1 cells, VD2 cells and VD3. Studies shows that the TRGC2 / TRDC selective A03 anti-constant domain antibody exhibits a significant lower binding signal to VD2 cells whilst the anti-TRGC1 / TRDC selective A10 clone exhibits a significantly lower binding profile for VD1 or VD3 cells. Finally, the A09, A12 and A14 clones which can selectively bind TRGC1 / TRDC and TRGC2 / TRDC bind all VD1, VD2 and VD3 subsets similarly (C) Cytotoxicity assays involving gamma delta cells co-incubated with THP-1 cells plus test antibodies as indicated. Lefthand study used gamma delta effector cells more enriched for VD1 cells as indicated in the upper bar chart. The righthand study used gamma delta effector cells similarly enriched for VD1 5 and VD2 cells, again see upper bar chart. Study shows that the more selective A03 and A10 anti- constant domain antibodies are inferior relative to true-pan binders able to bind all gamma delta cells similarly and that the degree of inferiority may be impacted by the VD1 / VD2 / VD3 ratio of the gamma delta effector cells employed in the assay. 10 Figure 25: AlphaFold modelling of antibody / antigen engagement: (A) A static model of the full length TCR / CD3 complex including the position of example loops located on the ‘shoulder’ TRGC / TRDC complex (B). Modelling approach undertaken to model antibody engagement with isolated Ig-like domains Vh: Vl: TRGC: TRDC engagement using AlphaFold (C) Model of isolated TRGC1 / TRDC Ig-like domain including position of BC / FG loop shoulder and more C-terminal G-sheet flanking regions.15Figure 26: Binding profile comparison of anti-TRGC1 / TRDC selective antibodies vs broader anti- TRGC1 / TRGC2 selective antibodies. In each graph, anti-TRGC1 / TRGC2 selective antibodies (black and dark grey coloured bars – A09 and A14)) flank the more anti-TRGC1 only biased antibody (light grey bars - A10) in the middle (A) Binding to primary gamma delta T-cells (left-hand bar chart) (B) Binding 20 to human gamma delta TRGC2 positive PEER cell line (right-hand bar chart). Figure 27: Attempted TRGC1 / TRDC and TRGC2 / TRDC deglycosylation. Attempted native (non- denaturing) deglycosylation of Ant01 and Ant04. Top row Ant01; bottom row Ant04. The major peak identified via LC-MS analysis is indicated by circle for each analysis. Left hand columns: LC-MS analysis 25 of starting antigen. Middle column LC-MS analysis of control deglycosylated, denatured antigen: Right column LC-MS analysis of (attempted) deglycosylated, non-denatured antigen – only TRGC1 / TRDC antigen is successfully deglycosylated under more native or non-denaturing conditions thereby further highlighting the differences between TRGC1 / TRDC and TRGC2 / TRDC antigens as provided herein and the importance of considering use of both such antigens in the methods of the invention. 30 Figure 28: Comparative binding profile of antibodies against primary (mixed) gamma delta T-cells, or VD1, or VD2, or VD3 sub-gated populations. Bar chart summaries presented. TRGC1 biased clones generated from a prior campaign (CYTA161, CYTA163 and CYTA165) and TRGC1 and TRGC2 ‘true pan’ specific clones (CYTA115 and R10) identified using antigens provided herein. Bar chart orientation: binding to mixed human gamma delta enriched PBMCs (top, far left), VD1 positive sub-gate (top, second from left VD2), VD2 positive sub-gate (top, far right), VD3 sub-gate (bottom, left), and alpha- beta sub-gate (bottom, right). Figure highlights that the TRGC1-biased clones underperform when targeting VD1 and VD3 sub-gates thereby highlighting the preference of VD1 and VD3 cells for use of 5TRGC2.Figure 29: Example discovery campaign output: Lefthand flow diagram represents an example prior campaign employing antigens we believe comprised variable domains (represented by the 1HXM crystal structure). In this campaign, all selected antibodies generated were characterized as either10 variable domain selective, or likely constant / part variable domain selective, or proven TRGC1 / TRDC- biased by research herein. Righthand flow diagram represents our example campaign which employs antigens not containing variable domain. Via this constant domain centric approach, all selected binders discovered are not selective for the variable domain and a most preferred subset exhibit significantly less TRGC1 or TRGC2 bias. As such this class can be termed true-pan or universal binders 15 given they are characterized as selective for human TRGC1 containing TCRs and human TRGC2 containing TCRs (and cynomolgus TCR). Figure 30: Example of TRGC2 / TRDC selective bias or binding profile: Sequences and alignment highlights the extended Vh CDR3 of A03 inclusive of non-canonical cysteines. Also shown are three 20 daughter molecules (A037, A038 and A039) wherein these non-canonical cysteines are removed by different mutational strategies. Also included in this study is an anti-RSV antibody as a negative control. The X / Y plots below the alignment show titration (X axis) of the A03 antibody or mutated daughter molecules against primary gamma delta cells (mixed ‘pan’ population) or VD1 or VD2 or VD3 gated subsets as indicated Y axis indicated MFI as measured by flow-based analysis (with aid of a secondary 25 labelling anti-Ig antibody). First, these results further highlight the finding that the A03 molecule exhibits a very significant binding bias towards VD1 and VD3 subsets – these subsets typically contain more TRGC2+ve TCRs. Second it demonstrates that all attempts to remove the non-canonical cysteines failed and ablated all binding. 30 DETAILED DESCRIPTION OF THE INVENTION Before the various embodiments are described, it is to be understood that this disclosure is not limited to the particular embodiments described, and as such can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present teachings will be limited only by the appended claims. The section headings used herein are for organizational purposes only and are not to be construed as 5 limiting the subject matter described in any way. While the present teachings are described in conjunction with various embodiments, it is not intended that the present teachings be limited to such embodiments. On the contrary, the present teachings encompass various alternatives, modifications, and equivalents, as will be appreciated by those of skill in the art. 10 Unless defined otherwise, 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 disclosure belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure, some exemplary methods and materials are now described. 15 As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which can be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present teachings. Any recited method can be carried 20 out in the order of events recited or in any other order which is logically possible. All patents and publications, including all sequences disclosed within such patents and publications, referred to herein are expressly incorporated by reference. Numeric ranges are inclusive of the numbers defining the range. Unless otherwise indicated, nucleic 25 acids are written left to right in 5' to 3' orientation; amino acid sequences are written left to right in amino to carboxy orientation, respectively. Unless defined otherwise, 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. Still, certain 30 terms are defined below for the sake of clarity and ease of reference. It must be noted that as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. For example, the term “an antigen” refers to one or more antigens, i.e., a single antigen and multiple antigens. It is further noted that the claims can be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation. 5 The term “about” as used herein includes up to and including 10% greater and up to and including 10% lower than the value specified, suitably up to and including 5% greater and up to and including 5% lower than the value specified, especially the value specified. The term “between”, includes the values of the specified boundaries. 10 ANTIBODIES OF THE INVENTION The present invention provides an antibody or antigen-binding fragment thereof that specifically binds to one or more constant domains of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof. In preferred embodiments the antibody is a human antibody. 15 In a first aspect, the invention provides an antibody or antigen-binding fragment thereof that specifically binds to human TRGC2 / TRDC heterodimeric constant domain antigen, wherein the antibody or antigen-binding fragment thereof is a human antibody or antigen-binding fragment thereof. In some embodiments, the antibodies or antigen-binding fragments thereof also specifically 20 binds to human TRGC1 / TRDC heterodimeric constant domain antigen. The term “antibody” as used herein may be used interchangeably with term “immunoglobulin” or “Ig” and means an immunoglobulin molecule that recognizes and specifically binds to a target, such as a protein, polypeptide, peptide, carbohydrate, polynucleotide, lipid, or combinations of the foregoing 25 through at least one antigen recognition site within the variable region of the immunoglobulin molecule. As used herein, the term “antibody” encompasses intact polyclonal antibodies, intact monoclonal antibodies, antibody fragments (such as Fab, Fab', F(ab')2, and Fv fragments), single chain Fv (scFv) mutants, chimeric antibodies, fully human antibodies, humanized antibodies, fusion proteins comprising an antigen determination portion of an antibody, and any other modified immunoglobulin 30 molecule comprising an antigen recognition site so long as the antibodies exhibit the desired biological activity. The term “antibody” can also refer to a Y-shaped glycoprotein with a molecular weight of approximately 150 kDa that is made up of four polypeptide chains: four polypeptide chains: two heavy (H) chains and two light (L) chains. Each chain is divided into a constant region and a variable domain. The heavy (H) chain variable domains are abbreviated herein as VH, and the light (L) chain variable 35 domains are abbreviated herein as VL. These domains, domains related thereto and domains derived therefrom, may be referred to herein as immunoglobulin chain variable domains. The VH and VL domains (also referred to as VH and VL regions) can be further subdivided into regions, termed “complementarity determining regions” (“CDRs”), interspersed with regions that are more conserved, termed “framework regions” (“FRs”). The framework and complementarity determining regions have 5 been precisely defined (Kabat et al. Sequences of Proteins of Immunological Interest, Fifth Edition U.S. Department of Health and Human Services, (1991) NIH Publication Number 91-3242). There are also alternative numbering conventions for CDR sequences, for example those set out in Chothia et al. (1989) Nature 342: 877-883 or as summarized by IMGT.org. For guidance, antibody CDRs herein are defined by Kabat. However these CDR sequences are non-limiting. An ordinarily skilled person will be 10 able to define CDRs by alternative standard definitions. Open-access freeware such as provided by abysis.org and the like can be routinely employed to aid with such definitions. Typically by alternate definitions, a specific CDR may be the same, or marginally longer or shorter by sequence length. An ordinarily skilled person will readily recognize that regardless of which convention is employed to define a CDR, it is essentially the same CDR. In a conventional antibody, each VH and VL is composed 15 of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The conventional antibody tetramer of two heavy immunoglobulin chains and two light immunoglobulin chains is formed with the heavy and the light immunoglobulin chains inter-connected by e.g. disulphide bonds, and the heavy chains similarly connected. The whole antibody thus comprises two Fabs, each Fab comprising a VH-VL domain pair. 20 The heavy chain constant region includes three domains, CH1, CH2 and CH3. The light chain constant region is comprised of one domain, CL. The variable domain of the heavy chains and the variable domain of the light chains are binding domains that interact with an antigen. The constant regions of the antibodies typically mediate the binding of the antibody to host tissues or factors, including various cells of the immune system (e.g. effector cells) and the first component (C1q) of the classical 25 complement system. This also includes antibodies comprising an Fc region that has been engineered to contain antigen-binding loops in its CH3 domain - this modified Fc region is termed an "Fcab" (Fc with antigen binding). Antibodies may be oligoclonal, polyclonal, monoclonal (including full-length monoclonal antibodies), camelised, chimeric, CDR-grafted, single-domain, catalytic, chimeric, humanized, anti-idiotypic, including antibodies that can be labelled in soluble or bound form as well 30 as fragments, variants or derivatives thereof, either alone or in combination with other amino acid sequences provided by known techniques. An antibody may be from any species. A “human antibody” or “fully human antibody” refers to antibodies derived from human germline immunoglobulin sequences. Human antibodies provoke less cross-species antibody responses when administered to a human subject. The CDR, framework and / or constant region of the antibody or antigen-binding fragment thereof may be derived from a human Ig sequence, in particular a human IgG sequence. Human antibodies may include some amino acid residues not encoded by human germline immunoglobulin sequences (e.g. mutations introduced by random or site-specific mutagenesis or by somatic mutation). However, the term is not intended to include antibodies in which CDR sequences 5 derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences. An advantage of using human antibodies is that they are low or non- immunogenic in humans. Antibodies or antigen-binding fragments thereof can be naked or conjugated to other molecules such 10 as toxins, radioisotopes, etc. “EU numbering” refers to a numbering convention used for the numbering of amino acid residues in antibodies. Each residue of the antibody is assigned a number to allow comparison of antibodies. Where a variant antibody contains a residue that was not present in the wildtype antibody (e.g. an 15 insertion mutation) decimals are used to indicate the insertion. For example, if a residue was inserted between the residues designated numbers 1 and 2, the new residue would be given the EU number 1.1. EU numbering is an alternative numbering scheme to others such as Kabat, (Kabat et al. Sequences of Proteins of Immunological Interest, Fifth Edition U.S. Department of Health and Human Services, (1991) NIH Publication Number 91-3242). Chothia (Chothia et al. (1989) Nature 342: 877-883) or as 20 summarized by IMGT.org. wherein EU numbering is presented with further cross reference to Edelman, G.M. et al., Proc. Natl. Acad. USA, 63, 78-85 (1969). (10.1073 / pnas.63.1.78). The term “epitope” as used herein refers to a localised region of the antigen or target which is specifically bound by the antibody or antigen-binding fragment thereof. Epitopes usually consist of 25 chemically active surface groupings of molecules such as amino acids or sugar side chains and have specific three-dimensional structural characteristics as well as specific charge characteristics. Epitopes found on protein targets may be defined as “linear epitopes” or “conformational epitopes”. Linear epitopes are formed by a continuous or semi-continuous sequence of amino acids in a protein antigen. Conformational epitopes are formed of amino acids that are discontinuous in the protein sequence, 30 but which are brought together upon folding of the protein into its three-dimensional structure. Epitopes may also be referred to as “antigenic determinants”. An antibody binds “essentially the same epitope” as another antibody when they both recognize and bind identical or sterically overlapping epitopes. Commonly used methods to determine whether two antibodies bind to identical or overlapping epitopes are competition assays, which can be configured in a number of different formats (e.g. well plates using radioactive or enzyme labels, or flow cytometry on antigen-expressing cells) using either labelled antigen or labelled antibody. An antibody binds “the same epitope” as another antibody when they both recognize and bind identical epitopes (i.e. all contact points between the antigen and the antibody are the same). Various techniques are known in the art to establish which 5 epitope is bound by an antibody. Exemplary techniques include, for example, routine cross-blocking assays, antibody “binning”, alanine scanning mutational analysis, peptide blot analysis, peptide cleavage analysis crystallographic studies and NMR analysis. In addition, methods such as epitope excision, epitope extraction and chemical modification of antigens can be employed. Another method that can be used to identify the amino acids within a polypeptide with which an antibody interacts is 10 hydrogen / deuterium exchange detected by mass spectrometry. In general terms, the hydrogen / deuterium exchange method involves deuterium-labelling the protein of interest, followed by binding the antibody to the deuterium-labelled protein. Next, the protein / antibody complex is transferred to water and exchangeable protons within amino acids that are protected by the antibody complex undergo deuterium-to-hydrogen back-exchange at a slower rate than exchangeable protons 15 within amino acids that are not part of the interface. As a result, amino acids that form part of the protein / antibody interface may retain deuterium and therefore exhibit relatively higher mass compared to amino acids not included in the interface. After dissociation of the antibody, the target protein is subjected to protease cleavage and mass spectrometry analysis, thereby revealing the deuterium-labelled residues which correspond to the specific amino acids with which the antibody 20 interacts. A “Fab region” as used herein refers to a portion of an antibody (or constructs that contain said portion) comprising a VH-VL domain pair providing an antigen-binding site (also known as a CDR based antigen binding site). The Fab region may further comprise the CL and CH1 domains. A conventional antibody 25 with two heavy and two light chains thus comprises two Fabs, each Fab comprising a VH-VL domain pair. A “Fc region” (fragment crystallizable region), as used herein refers to a portion of an antibody (or constructs that contain said portion) comprising the CH2 and CH3 domains, optionally including hinge30 region too. The Fc region is the C-terminal region of an immunoglobulin heavy chain, including wild- type-sequence Fc regions and modified Fc regions. An Fc region is dimeric and thus comprises paired heavy chain constant regions each comprising a CH2 and CH3 domain. The term “specificity” as used herein is the ability of an antibody or antibody binding domain to recognise a particular antigen as a unique molecular entity and distinguish it from another. Specificity therefore refers to the number of different types of antigens or antigenic determinants to which a particular antibody or antigen-binding fragment thereof can bind. An antibody that “specifically binds” 5 to an antigen or an epitope is a term well understood in the art. A molecule is said to exhibit “specific binding” if it reacts more frequently, more rapidly, with greater duration and / or with greater affinity with a particular target antigen or epitope, than it does with alternative targets. An antibody that specifically binds to a particular epitope over another epitope may also be said to “selectively bind” to the first epitope. An antibody “specifically binds” to a target antigen or epitope if it binds with greater 10 affinity, avidity, more readily, and / or with greater duration than it binds to other substances. In one embodiment, the extent of binding of an antibody to an unrelated target is less than about 10% of the binding of the antibody to the target as measured, e.g. by a radioimmunoassay (RIA) or ELISA. As described above, gamma (^) delta (^) T-cell Receptors (gamma delta TCRs) are heterodimeric 15 receptors comprising a gamma chain and a delta chain. The gamma chain and the delta chain each comprise a variable region and a constant region, and the classification of the various chains is explained in detail above in the section headed “Gamma Delta TCRs”. An antibody “fragment” (also referred to as “antigen-binding fragment”) refers to a part of an antibody 20 that binds to the intended target even though it is not a full immunoglobulin chain. For example, the following non-exhaustive list includes examples of antigen-binding fragments of an antibody: (i) a Fab fragment (a monovalent fragment consisting of the VL, VH, CL and CH1 domains); (ii) a F(ab')2 fragment (a bivalent fragment consisting of two Fab fragments linked by a disulphide bridge at the hinge region); 25 (iii) a Fd fragment (consisting of the VH and CH1 domains); (iv) a Fv fragment (consisting of the VL and VH domains of a single arm of an antibody); (v) a single chain variable fragment, scFv (consisting of VL and VH domains joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules); 30 (vi) a VH (an immunoglobulin chain variable domain consisting of a VH domain); (vii) a VL (an immunoglobulin chain variable domain consisting of a VL domain); (viii) a domain antibody (dAb, consisting of either the VH or VL domain); (ix) a minibody (consisting of a pair of scFv fragments which are linked via CH3 domains); and (x) a diabody (consisting of a noncovalent dimer of scFv fragments that consist of a VH domain from one antibody connected by a small peptide linker a VL domain from another antibody). In some embodiments, the antigen-binding fragment is not a VHH domain or single domain antibody. 5 Antibodies or antigen-binding fragments thereof of the invention may be of any class. For example, they may be IgG, IgA, IgM, IgE, IgD or isotypes thereof. Antibodies and antigen-binding fragments thereof of the invention may comprise a kappa light chain or a lambda light chain. In some embodiments, the antibody or antigen-binding fragment thereof is an IgG antibody, such as an IgG2, 10 IgG3, IgG4 or preferably an IgG1 antibody. In some embodiments, the antibody or antigen-binding fragment thereof comprises a hinge disabled Fc region. In some embodiments, the antibody or antigen-binding fragment thereof comprises L235A and G237A mutations (according to Eu numbering). 15 In some embodiments, the antibody or antigen-binding fragment thereof of the invention comprises a VH and VL domain. In some embodiments, the CDRs (as defined by any applicable scheme such as for example Kabat, Eu, 20 IMGT, Chothia) of the antibody or antigen-binding fragment thereof of the invention do not comprise a cysteine. In some embodiments, the antibody or antigen-binding fragment does not comprise a non-canonical cysteine-cysteine bridge or disulfide bond 25 In some embodiments, the constant domain bound by the antibody or antigen-binding fragment is TRDC or a fragment thereof and / or TRGC1 or a fragment thereof and / or TRGC2 or a fragment thereof. In some embodiments, the constant domain bound by the antibody or antigen-binding fragment 30 thereof is TRDC or a fragment thereof. The constant domain may be human TRDC, or cyno TRDC, or murine TRDC, preferably human TRDC. In some embodiments, the constant domain bound by the antibody or antigen-binding fragment thereof is TRGC1 or a fragment thereof. The constant domain may be human TRGC1, or cyno TRGC, or murine TRGC1, preferably human TRGC1. 5 In some embodiments, the constant domain bound by the antibody or antigen-binding fragment thereof is TRGC2 or a fragment thereof. The constant domain may be human TRGC2, or cyno TRGC, or murine TRGC2, preferably human TRGC2. In some embodiments, the constant domains bound by the antibody or antigen-binding fragment 10 thereof are TRGC1 or a fragment thereof and TRGC2 or a fragment thereof. In some embodiments, the constant domains bound by the antibody or antigen-binding fragment thereof are TRGC1 or a fragment thereof and TRGC2 or a fragment thereof and not TRDC. The constant domains may be human TRGC1, or cyno TRGC, or murine TRGC1, and human TRGC2, or cyno TRGC, or murine TRGC2, preferably human TRGC1 and human TRGC2. 15 In some embodiments, the antibody or antigen-binding fragment thereof specifically binds to a first antigen wherein a first subunit of the first antigen comprises the amino acid sequence of SEQ ID NO: 10; and the second sub-unit of the first antigen comprises the amino acid sequence of SEQ ID NO: 11 and the antibody or antigen-binding fragment thereof specifically binds to a second antigen wherein 20 a first subunit of the second antigen comprises the amino acid sequence of SEQ ID NO: 10; and the second sub-unit of the first antigen comprises the amino acid sequence of SEQ ID NO: 12. In some embodiments, the antibody or antigen-binding fragment thereof binds a human constant domain or fragment thereof, or a cyno constant domain or fragment thereof, or a murine constant 25 domain or fragment thereof. The term “human constant domain” or “cyno constant domain” or “murine constant domain” refers to the constant domain of a gdTCR derived from humans, cynomolgus monkeys or mice, respectively. In some embodiments, the antibody or antigen-binding fragment thereof bind to a human constant domain or fragment thereof and does not bind to a murine constant domain or fragment thereof. In some embodiments, the antibody or antigen-binding 30 fragment thereof binds to a human constant domain and is “cross-reactive” with a cyno constant domain. As used herein, “cross-reactive” means the antibody or antigen-binding fragment thereof binds to a human constant domain or fragment thereof and a corresponding cyno constant domain or fragment thereof. Cross-reactivity is useful in providing antibodies that can be used for pre-clinical evaluation, for example in in vivo animal studies, which is an important step in medicine development. In some embodiments, the antibody or antigen-binding fragment thereof binds to corresponding human and cyno constant domains, for example the delta constant domain or the gamma constant domains. In some embodiments the antibody or antigen-binding fragment thereof binds to human TRDC or fragment thereof and cyno TRDC or fragment thereof. In some embodiments, the antibody or 5 antigen-binding fragment thereof binds human TRGC1 or fragment thereof and cyno TRGC or fragment thereof. In some embodiments, the antibody or antigen-binding fragment thereof binds human TRGC2 or fragment thereof and cyno TRGC or fragment thereof. In some embodiments, the antibody or antigen-binding fragment thereof binds human TRGC1 or fragment thereof, human TRGC2 or fragment thereof, and cyno TRGC or fragment thereof. 10 In some embodiments, the antibody or antigen-binding fragment thereof does not bind to a variable domain of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof. In some embodiments, antibodies or antigen-binding fragments thereof specifically bind to; 15 a. antigens comprising gdTCR constant domain sequences (SEQ ID NOs: 1 to 20) which do not also contain any V-D-J region sequence or sequences as outlined in Table 7 (SEQ ID NOs: 66 to 83) and; b. antigens comprising gdTCR constant domain sequence (SEQ ID NOs: 1 to 20) which do also contain V-D-J region sequence or sequences as outlined in Table 7 (SEQ ID NOs: 66 to 83); 20 but which do not specifically bind; c. antigens containing gdTCR V-D-J sequence or sequences as outlined in Table 7 (SEQ ID Nos: 66 to 83) which do not also comprise gdTCR constant domain sequence (SEQ ID NOs: 1 to 20) 25 In this embodiment therefore the antibody or antigen-binding fragment thereof identified specifically binds only to the constant domain and does not bind to any sequence in the variable region. In some embodiments, the antibody or antigen-binding fragment thereof is able to specifically bind to 30 more than one constant domain. In some embodiments, the antibody or antigen-binding fragment thereof specifically binds to both TRGC1 and TRGC2. In some embodiments, the antibody or antigen- binding fragment thereof specifically binds to TRGC1 and TRGC2 and TRDC. In some embodiments, the antibody or antigen-binding fragment thereof specifically binds to both TRGC1 and TRDC. In some embodiments, the antibody or antigen-binding fragment thereof specifically binds to both TRGC2 and TRDC. In some embodiments, the antibody or antigen-binding fragment thereof specifically binds to both TRGC1 and TRGC2 and not TRDC. In some embodiments, the antibody or antigen-binding fragment thereof specifically binds to an 5 antigen comprising or consisting of SEQ ID NO: 3 (optionally a fragment thereof comprising residues Lys11 to Phe105 of SEQ ID NO: 3). In some embodiments, the antibody or antigen-binding fragment thereof specifically binds to an antigen comprising or consisting of SEQ ID NO: 2 (optionally a fragment thereof comprising residues Lys11 to Phe105 of SEQ ID NO: 3). 10 In some embodiments, the antibody or antigen-binding fragment thereof preferentially binds to one constant domain over another, or may specifically bind to only one constant domain. In some embodiments, the antibody or antigen-binding fragment thereof preferentially binds to TRGC1 over TRGC2. As used herein, “preferentially binds” means the antibody or antigen-binding 15 fragment binds more specifically to TRGC1 than it does to TRGC2. In some embodiments, the antibody or antigen-binding fragment thereof has an affinity for TRGC1 antigen that is 2-fold; or 5-fold; or 10- fold; or 50-fold; or 100-fold; or 500-fold; or 1000-fold greater than the affinity for TRGC2 antigen when measured under the same or substantially the same conditions. In some embodiments, the antibody or antigen-binding fragment thereof has an affinity for TRGC1 antigen that is 10-fold greater than the 20 affinity for TRGC2 antigen when measured under the same or substantially the same conditions. Affinity can be measured by any method know in the art, for example as measured using surface plasmon resonance. In some embodiments, the antibody or antigen-binding fragment thereof specifically binds to TRGC1 and does not specifically bind to TRGC2. 25 In some embodiments, the antibody or antigen-binding fragment thereof preferentially binds to TRGC2 over TRGC1. As used herein, “preferentially binds” means the antibody or antigen-binding fragment binds more specifically to TRGC2 than it does to TRGC1. In some embodiments, the antibody or antigen-binding fragment thereof has an affinity for TRGC2 antigen that is 2-fold; or 5-fold; or 10- fold; or 50-fold; or 100-fold; or 500-fold; or 1000-fold greater than the affinity for TRGC1 antigen when 30 measured under the same or substantially the same conditions. In some embodiments, the antibody or antigen-binding fragment thereof has an affinity for TRGC2 antigen that is 10-fold greater than the affinity for TRGC1 antigen when measured under the same or substantially the same conditions. Affinity can be measured by any method know in the art, for example as measured using surface plasmon resonance. In another embodiment, the antibody or antigen-binding fragment thereof of specifically binds to TRGC2 and does not specifically bind to TRGC1. The antibodies or antigen-binding fragments thereof of this invention are capable of selectively 5 recognising constant domains structures present in authentic heterodimeric GC1 and GC2 TCRs expressed on the surface of a T cell. Said antibodies are not dependent on contact points found elsewhere in either the N-terminal variable and VDJ domains of the receptor, or in less structured, more varied sequence found in the more C-terminal section of the constant domain. Known antibodies that bind to gamma delta TCRs may therefore be inferior in this regard. For example, it has previously 10 been demonstrated that rodent-generated so-called pan antibodies such as IMMU510 partially compete with rodent generated so-called anti-VD1 specific antibodies such as TS8.2 (e.g. see Figure 6 of WO17197347). Logically such competition is only possible if these two antibodies are at least partially dependent and competing for space or contact points in the intervening J- region. The presently provided antibodies are not dependent on nor do they bind to the J region. Hence in one 15 embodiment antibodies as provided herein can still bind TRDC or TRGC constant domain sequence in the presence of IMMU510. In one embodiment antibodies provided herein do not compete with IMMU510. In some embodiments, the antibody or antigen-binding fragment thereof preferentially binds to TRDC 20 over TRGC1 or TRGC2. As used herein, “preferentially binds” means the antibody or antigen-binding fragment binds more specifically to TRDC than it does to TRGC1 or TRGC2. In some embodiments, the antibody or antigen-binding fragment thereof has an affinity for TRDC antigen that is 2-fold; or 5-fold; or 10-fold; or 50-fold; or 100-fold; or 500-fold; or 1000-fold greater than the affinity for TRGC1 antigen or TRGC2 antigen when measured under the same or substantially the same conditions. In some 25 embodiments, the antibody or antigen-binding fragment thereof has an affinity for TRDC antigen that is 10-fold greater than the affinity for TRGC1 antigen or TRGC2 antigen when measured under the same or substantially the same conditions. Affinity can be measured by any method know in the art, for example as measured using surface plasmon resonance. 30 In one embodiment, the antibody or antigen-binding fragment thereof specifically binds to TRDC and does not bind specifically to TRGC1 or TRGC2. In some embodiments, the antibodies or antigen-binding fragments thereof bind to protein sequences common to both human TRDC / TRGC1 and human TRDC / TRGC2 heterodimeric complexes. For example, a TRDC sequence or a sequence that appears in both TRGC1 and TRGC2. See Figure 4 which shows alignment and identities of TRGC domains. In some embodiments, the antibodies or antigen-binding fragments thereof specifically bind to (i) 5 human TRGC2 / TRDC heterodimeric constant domain antigen, (ii) human TRGC1 / TRDC heterodimeric constant domain antigen and cynomolgus TRGC / TRDC constant domain antigen. In some embodiments, the antibodies or antigen-binding fragments thereof specifically bind to (i) glycosylated recombinant human TRGC2 / TRDC heterodimeric constant domain antigen, (ii) 10 glycosylated recombinant human TRGC1 / TRDC heterodimeric constant domain antigen and glycosylated recombinant cynomolgus TRGC / TRDC constant domain antigen. In some embodiments, the invention provides an antibody or antigen-binding fragment thereof that specifically binds to one or more constant domains of a gamma delta T-cell receptor (gdTCR) or a 15 fragment or fragments thereof and does not specifically bind to a variable domain of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof, wherein the antibody or antigen-binding fragment thereof is a human antibody or antigen-binding fragment thereof. In some embodiments, the antibody or antigen-binding fragment thereof specifically binds human TRDC or a fragment thereof and does not specifically bind to a variable domain of a gamma delta T-cell receptor (gdTCR) or a 20 fragment or fragments thereof. In some embodiments, the antibody or antigen-binding fragment thereof specifically binds human TRGC1 or a fragment thereof and does not specifically bind to a variable domain of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof. In some embodiments, the antibody or antigen-binding fragment thereof specifically binds human TRGC2 or a fragment thereof and does not specifically bind to a variable domain of a gamma delta T-cell receptor 25 (gdTCR) or a fragment or fragments thereof. In some embodiments, the antibodies or antigen-binding fragments thereof do not specifically bind to: ^ a Fc region 30 ^ a gdTCR transmembrane sequence; ^ TRDC peri transmembrane sequence located C-terminal of position valine129 (SEQ ID NO:1); ^ TRGC1 peri transmembrane sequence located C-terminal of position alanine138 (SEQ ID NO:2); ^ TRGC2 peri transmembrane sequence located C-terminal of alanine154 (SEQ ID NO:3); ^ ‘connecting region’ of the gdTCR antigen located downstream and C-terminal of position Ser109 (for TRDC antigen), position Asn120 (for TRGC1) or position Asn136 (TRGC2) in the respective TRDC, TRGC1 or TRGC2 antigens; ^ the C-terminal constant domain sequences downstream of Ser109 (for TRDC antigen), 5 position Asn120 (for TRGC1) or position Asn136 (TRGC2) and the alpha-helix transmembrane. Such regions may be poorly recognised by antibodies, which should bind to the constant domain of the gdTCR only. 10 In some embodiments, the antibody or antigen-binding fragment is isolated. The term “isolated” as used herein means an antibody that has been removed from its original environment. An isolated antibody may be used to denote an antibody that is substantially free of other antibodies that bind to different antigens. For example, an isolated antibody that specifically binds one or more gamma constant domains is substantially free of antibodies that bind an antigen that is not a gamma constant 15 domain. The term “isolated” may also be used to refer to preparations where the isolated antibody is sufficiently pure to be administered therapeutically when formulated as an active ingredient of a pharmaceutical composition, or at least 70-80% (w / w) pure, more preferably, at least 80-90% (w / w) pure, even more preferably, 90-95% pure; and, most preferably, at least 95%, 96%, 97%, 98%, 99%, or 100% (w / w) pure. 20 Functional properties of antibodies of the invention The antibodies or antigen binding fragments of the present invention may have an advantageous functional profile. For example, antibodies or antigen-binding fragments thereof of the invention may selectively activate and / or induce proliferation of gamma delta T cells. Antibodies or antigen-binding fragments thereof of the invention may induce downregulation of gamma delta TCRs. Antibodies or 25 antigen-binding fragments thereof of the invention may induce, promote or increase gamma delta T cell mediated killing. As used herein “activation” of a gamma delta T cell refers to a change in the behaviour or morphology of the gamma delta T cell resulting from exposure to an activating factor. For example, in vivo a T cell 30 may be activated or stimulated by physical interaction of the TCR with an activating factor that is a cognate peptide presented by the major histocompatibility complex molecule expressed on the surface of an antigen-presenting cell. A gamma delta T cell can also be activated or stimulated by the physical interaction of the TCR with another activating factor, such as an antibody or antigen-binding fragment of the present invention. Changes in behaviour and morphology displayed during activation include TCR downregulation, growth and proliferation of T cells and / or effector functions such as cytokine secretion, cytotoxicity, degranulation, initiation of the cell based functions of the immune system or enzyme secretion. Activation of gamma delta T cells can be measured by any suitable method known in the art, for example quantification of T cell activation markers such as CD107a, CD25, 5 CD69 or Ki67 via flow cytometry. As used herein, “proliferation” of gamma delta T cells refers to an increase, growth or expansion of the number of gamma delta T cells as a result of cell division. Proliferation of gamma delta T cells can be measured by any suitable method known in the art that demonstrates a change in cell number over 10 time, for example using a hemacytometer counting chamber, using a multi-mode cell imager or assays that measure the change in metabolic activity of cells. As used herein, “downregulation” of gamma delta TCRs refers to the process in which activated TCRs are internalised by the T cell and retained or degraded as part of the T cell activation process. The TCRs 15 are therefore no longer displayed on the cell surface. TCR downregulation may be a marker of T cell activation. TCR downregulation may be measured by any suitable method known in the art, such as measuring TCR expression using median fluorescence intensity measured by flow cytometry. As used herein, “gamma delta T cell mediated cell killing” refers to direct killing of tumor or cancer 20 cells by gamma delta T cells, for example via cytotoxic functions such as secretion of perforin or granzymes by a gamma delta T cell that has recognised a tumor or cancer cell. This is distinct from ADCC (antibody-dependent cell-mediated cytotoxicity) which refers to a cell-mediated process of killing which occurs when an immune effector cell recognises cell bound antibodies and triggers lysis and death of the target cell, typically mediated via Fc-Fcγ interactions. Antibodies or antigen-binding 25 fragments thereof of the invention may induce, promote or increase gamma delta T cell mediated killing upon binding to a gamma delta T cell. Such gamma delta T cell mediated killing does not occur via ADCC cell-mediated mechanisms. Gamma delta T cell mediated killing can be measured by any suitable method known in the art, for example target cells (such as cancer or tumor cells) may be incubated with gamma delta T cells in the presence of the antibody or antigen-binding fragment 30 thereof of the invention. After incubation, the cell culture can be stained with a dye to distinguish between target cells that are dead or alive and the proportion of dead cells can then be measured, for example by flow cytometry methods. In some embodiments, the antibody or antigen-binding fragment thereof of the invention specifically binds to multiple different delta chains of the gamma delta TCR, for example delta 1 positive, delta 2 positive, delta 3 positive, delta 4 positive, delta 5 positive, delta 6 positive, delta 7 positive and / or delta 8 positive gamma delta TCRs. In some embodiments, the antibody or antigen-binding fragment thereof 5 of the invention specifically binds to delta 1 positive and delta 2 positive and delta 3 positive gamma delta TCRs. In some embodiments, the antibody or antigen-binding fragments of the invention downregulates delta 1 positive and delta 2 positive and delta 3 positive gamma delta TCRs. In some embodiments, the antibody or antigen-binding fragments of the invention selectively activates and / or induces proliferation of delta 1 positive and delta 2 positive and delta 3 positive gamma delta cells. 10 The proliferation and / or downregulation may occur in all three cell subtypes concurrently, meaning delta 1 positive and delta 2 positive and delta 3 positive gamma delta cells can all be activated in parallel by antibodies of the invention. In some embodiments, the antibody or antigen-binding fragment thereof of the invention specifically 15 binds to multiple different gamma chains of the gamma delta TCR. In some embodiments, the antibody or antigen-binding fragment thereof of the invention specifically binds gamma 4 positive and gamma 9 positive gamma delta TCRs. In some embodiments, the antibody or antigen-binding fragment thereof of the invention selectively activates and / or induces proliferation of gamma 4 positive and gamma 9 positive gamma delta T cells. In some embodiments, the antibody or antigen-binding 20 fragment thereof of the invention selectively activates and / or induces proliferation of blood resident gamma delta cells, optionally gamma 9 positive gamma delta cells or delta 2 positive gamma delta cells; and also selectively activates and / or induces proliferation of tissue resident gamma delta cells, optionally delta one positive gamma delta cells or delta 3 positive gamma delta cells. 25 In some embodiments, the antibody or antigen-binding fragment thereof of the invention binds delta 1 positive and delta 2 positive and delta 3 positive gamma delta TCRs derived from peripheral blood mononuclear cells (PBMCs). In some embodiments, the antibody or antigen-binding fragment thereof of the invention binds to 30 immortalized cells expressing TRGC2 containing TCR (for example PEER cells). In some embodiments, the antibody or antigen-binding fragment thereof of the invention binds to PEER cells expressing TRGC2 containing TCR. PEER cells are identified by catalogue number ACC 6 in DSMZ, Leibniz Institute, Germany. In some embodiments, the antibody or antigen-binding fragment thereof of the invention induces proliferation and / or TCR downregulation of gamma constant 1 positive cells but not gamma constant 5 2 positive cells. For example, an anti-TRGC1 antibody will bind to TRGC1 and not to TRGC2 leading to TCR downregulation of TCRs comprising TRGC1 and not those comprising TRGC2 and / or proliferation of cells comprising TRGC1 positive TCRs and not those comprising TRGC2 positive TCRs. In some embodiments, the antibody or antigen-binding fragment thereof of the invention induces 10 proliferation and / or TCR downregulation of gamma constant 2 positive cells but not gamma constant 1 positive cells. For example, an anti-TRGC2 antibody will bind to TRGC2 and not to TRGC1 leading to TCR downregulation of TCRs comprising TRGC2 and not those comprising TRGC1 and / or proliferation of cells comprising TRGC2 positive TCRs and not those comprising TRGC1 positive TCRs. 15 In some embodiments, the antibody or antigen-binding fragment thereof of the invention induces a greater than 150-fold, 200-fold, 300-fold, 450-fold or 460-fold proliferation in the number of gamma delta T cells. In some embodiments, the antibody or antigen-binding fragment thereof of the invention induces a greater than 150-fold, 200-fold, 300-fold, 450-fold or 460-fold proliferation in the number of Vδ3 gamma delta T cells. 20 The TCR downregulation, T cell activation and / or T cell proliferation may take place when the antibodies or antigen-binding fragments of the invention are administered to gamma delta T cells in human blood, a human blood sample or derived cells or when administered to a patient. 25 The antibodies or antigen-binding fragments of the invention target all γδ T cells, both blood and tissue resident. This differentiated technology enables circumvention of heterogeneity and fully enables γδ T cell activity across the broadest range of patients. Blood resident γδ T cells (typically Vδ2 enriched) are activated by antibodies of the invention, which may trigger cytokine release, immune licensing and migration of these γδ T cells out of blood circulation and into tumours. Tissue / tumour resident γδ T 30 cells (typically Vδ1 and Vδ3 enriched that may be tissue adapted e.g. to hypoxia) are also activated by antibodies of the invention, which may also trigger cytokine release, immune licensing and migration of these γδ T cells out of the tissues and into tumours. In some embodiments, the antibody or antigen-binding fragment thereof of the invention is an IgG1 antibody or fragment thereof and induces proliferation of gamma delta T cells. In some embodiments, the antibody or antigen-binding fragment thereof of the invention is an IgG1 antibody or fragment thereof and activates gamma delta T-cells to kill THP-1 cells in a co-culture assay. Sequences of antibodies and antigen-binding fragments thereof provided herein A summary of some of the antibodies and antigen-binding fragments thereof provided by the present invention is provided below with reference to the SEQ ID NO corresponding to the accompanying sequence listing. Sequences are provided in the attached sequence listing and the accompanying Figures. In the case of any discrepancy between the sequences in the sequence listing and those in Figure 18, the sequences in Figure 18 should prevail. In any aspect, the heavy chain constant domain of the antibody or antigen-binding fragment thereof may comprise or consist of the amino acid sequence of SEQ ID NO: 326 or 389. TABLE 3: Summary of provided antibodies and SEQ ID Nos Full Full Clone name VH VL HCDR1 HCDR2 HCDR3 LCDR1 LCDR2 LCDR3 heavy light chain chain Clone 6 94 95 152 153 154 155 156 157 329 330 Clone 38 96 97 158 159 160 161 162 163 331 332 Clone 128 98 99 164 165 166 167 168 169 333 334 Clone 205 100 101 170 171 172 173 174 175 335 336 Clone 228 102 103 176 177 178 179 180 181 337 338 Clone 303 104 105 182 183 184 185 186 187 339 340 Clone 325 106 107 188 189 190 191 192 193 341 342 Clone 332 108 109 194 195 196 197 198 199 343 344 Clone 487 110 111 200 201 202 203 204 205 345 346 Clone 489 112 113 206 207 208 209 210 211 347 348 Clone 525 114 115 212 213 214 215 216 217 349 350 Clone 545 116 117 218 219 220 221 222 223 351 352 Clone 567 118 119 224 225 226 227 228 229 353 354 Clone 578 120 121 230 231 232 233 234 235 355 356 Clone 641 122 123 236 237 238 239 240 241 357 358 Clone 676 124 125 242 243 244 245 246 247 359 360 Clone 680 126 127 248 249 250 251 252 253 361 362 Clone 697 128 129 254 255 256 257 258 259 363 364 Clone 717 130 131 260 261 262 263 264 265 365 366 Clone 731 132 133 266 267 268 269 270 271 367 368 Clone 734 134 135 272 273 274 275 276 277 369 370 Clone 745 136 137 278 279 280 281 282 283 371 372 Clone 759 138 139 284 285 286 287 288 289 373 374 Clone 811 140 141 290 291 292 293 294 295 375 376 Clone 894 142 143 296 297 298 299 300 301 377 378 Clone 953 144 145 302 303 304 305 306 307 379 380 Clone 957 146 147 308 309 310 311 312 313 381 382 Clone 1125 148 149 314 315 316 317 318 319 383 384 Clone 1171 150 151 320 321 322 323 324 325 385 386 Clone 6 (CYTA001): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 152; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 153; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 154; and / or a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 155; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 156; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 157. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 152, 153 and 154, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID Nos: 155, 156 and 157, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 94 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 5 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 95, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 10 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 94 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 95. 15 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 94 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 95. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant 20 domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise 25 or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 30 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 329 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 330. Any sequence variation may occur outside the CDR regions or outside the 5 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 329 and SEQ ID NO: 330. Clone 38 (CYTA002): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 10 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 158; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 15 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 159; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 160; and / or 20 a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 161; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 25 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 162; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 163. 30 In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 158, 159 and 160, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 161, 162 and 163, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 96 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence 5 identity to SEQ ID NO: 97, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 96 10 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 97. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or 15 consisting of the amino acid sequence of SEQ ID NO: 96 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 97. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human 20 heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may 25 be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain 30 comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 331 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 332. Any sequence variation may occur outside the CDR regions or outside the VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise 5 the amino acid sequences of SEQ ID NO: 331 and SEQ ID NO: 332. Clone 128 (CYTA003): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising a heavy chain variable region comprising: 10 a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 164; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at 15 least 99% or 100% identity to SEQ ID NO: 165; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 166; and / or a light chain variable region comprising: 20 a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 167; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at 25 least 99% or 100% identity to SEQ ID NO: 168; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 169. 30 In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 164, 165 and 166, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 167, 168 and 169, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 98 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 99, such that any sequence variations occur outside the CDR regions. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 98 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 10 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 99. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 98 and a VL comprising or consisting of the amino 15 acid sequence of SEQ ID NO: 99. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino 20 acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the 25 antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light 30 chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 333 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 334. Any sequence variation may occur outside the CDR regions or outside the VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 333 and SEQ ID NO: 334. 5 In some embodiments of this aspect, the antibody or antigen-binding fragment thereof specifically binds to human TRGC2 / TRDC heterodimeric constant domain antigen. In some embodiments of this aspect, the antibody or antigen-binding fragment thereof specifically 10 binds to human TRGC2 / TRDC heterodimeric constant domain antigen and specifically binds to cynomolgus TRGC / TRDC heterodimeric constant domain antigen. In some embodiments of this aspect, the antibody or antigen-binding fragment thereof promotes gamma delta T cell mediated killing (optionally THP-1 cell killing in co-culture assay). 15 In some embodiments of this aspect, the antibody or antigen-binding fragment thereof binds to PEER cells expressing TRGC2 positive TCRs. In some embodiments of this aspect, the antibody or antigen-binding fragment thereof specifically 20 binds to delta 1 positive and delta 3 positive gamma delta TCRs. In some embodiments of this aspect, the antibody or antigen-binding fragment thereof downregulates delta 1 positive and delta 3 positive gamma delta TCRs 25 In some embodiments of this aspect, the antibody or antigen-binding fragment thereof selectively activates and / or induces proliferation of delta 1 positive and delta 3 positive gamma delta cells. Clone 205 (CYTA004): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 30 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 170; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 171; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 172; and / or a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at 10 least 99% or 100% identity to SEQ ID NO: 173; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 174; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 15 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 175. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 170, 171 and 172, respectively, and 20 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 173, 174 and 175, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 100 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 25 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 101, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 30 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 100 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 101. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 100 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 101. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC 10 human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 15 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 20 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 335 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 336. Any sequence variation may occur outside the CDR regions or outside the 25 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 335 and SEQ ID NO: 336. Clone 228 (CYTA005): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 30 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 176; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 177; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 178; and / or a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at 10 least 99% or 100% identity to SEQ ID NO: 179; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 180; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 15 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 181. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 176, 177 and 178, respectively, and 20 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 179, 180 and 181, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 102 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 25 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 103, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 30 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 102 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 103. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 102 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 103. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC 10 human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 15 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 20 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 337 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 338. Any sequence variation may occur outside the CDR regions or outside the 25 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 337 and SEQ ID NO: 338. Clone 303 (CYTA006): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 30 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 182; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 183; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 184; and / or a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at 10 least 99% or 100% identity to SEQ ID NO: 185; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 186; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 15 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 187. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 182, 183 and 184, respectively, and 20 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 185, 186 and 187, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 104 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 25 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 105, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 30 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 104 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 105. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 104 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 105. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC 10 human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 15 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 20 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 339 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 340. Any sequence variation may occur outside the CDR regions or outside the 25 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 339 and SEQ ID NO: 340. Clone 325 (CYTA007): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 30 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 188; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 189; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 190; and / or a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at 10 least 99% or 100% identity to SEQ ID NO: 191; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 192; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 15 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 193. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 188, 189 and 190, respectively, and 20 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 191, 192 and 193, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 106 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 25 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 107, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 30 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 106 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 107. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 106 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 107. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC 10 human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 15 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 20 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 341 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 342. Any sequence variation may occur outside the CDR regions or outside the 25 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 341 and SEQ ID NO: 342. Clone 332 (CYTA008): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 30 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 194; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 195; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 196; and / or a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at 10 least 99% or 100% identity to SEQ ID NO: 197; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 198; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 15 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 199. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 194, 195 and 196, respectively, and 20 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 197, 198 and 199, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 108 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 25 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 109, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at 30 least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 108 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 109. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 108 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 109. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC 10 human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 15 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 20 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 343 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 344. Any sequence variation may occur outside the CDR regions or outside the 25 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 343 and SEQ ID NO: 344. Clone 487 (CYTA009): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 30 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 200; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 201; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 202; and / or a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at 10 least 99% or 100% identity to SEQ ID NO: 203; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 204; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 15 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 205. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 200, 201 and 202, respectively, and 20 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 203, 204 and 205, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 110 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 25 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 111, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at 30 least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 110 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 111. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 110 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 111. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC 10 human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 15 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 20 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 345 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 346. Any sequence variation may occur outside the CDR regions or outside the 25 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 345 and SEQ ID NO: 346. In some embodiments of this aspect, the antibody or antigen-binding fragment thereof specifically binds to human TRGC2 / TRDC heterodimeric constant domain antigen and specifically binds to human 30 TRGC1 / TRDC heterodimeric constant domain antigen. In some embodiments of this aspect, the antibody or antigen-binding fragment thereof specifically binds to human TRGC2 / TRDC heterodimeric constant domain antigen, specifically binds to human TRGC1 / TRDC heterodimeric constant domain antigen and specifically binds to cynomolgus TRGC / TRDC heterodimeric constant domain antigen. In some embodiments of this aspect, the antibody or antigen-binding fragment thereof promotes 5 gamma delta T cell mediated killing (optionally THP-1 cell killing in co-culture assay). In some embodiments of this aspect, the antibody or antigen-binding fragment thereof binds to PEER cells expressing TRGC2 positive TCRs. 10 In some embodiments of this aspect, the antibody or antigen-binding fragment thereof specifically binds to delta 1 positive and delta 2 positive and delta 3 positive gamma delta TCRs. In some embodiments of this aspect, the antibody or antigen-binding fragment thereof downregulates delta 1 positive and delta 2 positive and delta 3 positive gamma delta TCRs 15 In some embodiments of this aspect, the antibody or antigen-binding fragment thereof selectively activates and / or induces proliferation of delta 1 positive and delta 2 positive and delta 3 positive gamma delta cells. 20 Clone 489 (CYTA010): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at 25 least 99% or 100% identity to SEQ ID NO: 206; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 207; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 30 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 208; and / or a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 209; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 210; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 211. 10 In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 206, 207 and 208, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 209, 210 and 211, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an 15 amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 112 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 113, such that any sequence variations occur outside the CDR regions. 20 In this aspect the antibody or antigen-binding fragment thereof may a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 112 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at 25 least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 113. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 112 and a VL comprising or consisting of the 30 amino acid sequence of SEQ ID NO: 113. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may 5 be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain 10 comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 347 and / or an amino 15 acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 348. Any sequence variation may occur outside the CDR regions or outside the VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 347 and SEQ ID NO: 348. 20 In some embodiments of this aspect, the antibody or antigen-binding fragment thereof specifically binds to human TRGC1 / TRDC heterodimeric constant domain antigen. In some embodiments of this aspect, the antibody or antigen-binding fragment thereof specifically 25 binds to human TRGC1 / TRDC heterodimeric constant domain antigen and specifically binds to cynomolgus TRGC / TRDC heterodimeric constant domain antigen. In some embodiments of this aspect, the antibody or antigen-binding fragment thereof promotes gamma delta T cell mediated killing (optionally THP-1 cell killing in co-culture assay). 30 In some embodiments of this aspect, the antibody or antigen-binding fragment thereof specifically binds to delta 2 positive gamma delta TCRs. In some embodiments of this aspect, the antibody or antigen-binding fragment thereof downregulates delta 2 positive gamma delta TCRs In some embodiments of this aspect, the antibody or antigen-binding fragment thereof selectively 5 activates and / or induces proliferation of delta 2 positive gamma delta cells. Clone 525 (CYTA011): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising a heavy chain variable region comprising: 10 a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 212; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at 15 least 99% or 100% identity to SEQ ID NO: 213; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 214; and / or a light chain variable region comprising: 20 a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 215; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at 25 least 99% or 100% identity to SEQ ID NO: 216; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 217. 30 In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 212, 213 and 214, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 215, 216 and 217, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 114 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 115, such that any sequence variations occur outside the CDR regions. 5 In this aspect the antibody or antigen-binding fragment thereof may a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 114 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at 10 least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 115. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 114 and a VL comprising or consisting of the 15 amino acid sequence of SEQ ID NO: 115. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino 20 acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the 25 antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light 30 chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 349 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 350. Any sequence variation may occur outside the CDR regions or outside the VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 349 and SEQ ID NO: 350. 5 Clone 545 (CYTA012): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 10 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 218; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 219; and 15 a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 220; and / or a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 20 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 221; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 222; and 25 a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 223. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 30 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 218, 219 and 220, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 221, 222 and 223, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 116 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 117, such that any sequence variations occur outside the CDR regions. 5 In this aspect the antibody or antigen-binding fragment thereof may a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 116 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity 10 to SEQ ID NO: 117. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 116 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 117. 15 In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may 20 comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or 25 SEQ ID NO: 326 and SEQ ID NO: 328. In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or 30 antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 351 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 352. Any sequence variation may occur outside the CDR regions or outside the VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 351 and SEQ ID NO: 352. 5 In some embodiments of this aspect, the antibody or antigen-binding fragment thereof specifically binds to human TRGC2 / TRDC heterodimeric constant domain antigen and specifically binds to human TRGC1 / TRDC heterodimeric constant domain antigen. In some embodiments of this aspect, the antibody or antigen-binding fragment thereof promotes 10 gamma delta T cell mediated killing (optionally THP-1 cell killing in co-culture assay). In some embodiments of this aspect, the antibody or antigen-binding fragment thereof binds to PEER cells expressing TRGC2 positive TCRs. 15 In some embodiments of this aspect, the antibody or antigen-binding fragment thereof specifically binds to delta 1 positive and delta 2 positive and delta 3 positive gamma delta TCRs. In some embodiments of this aspect, the antibody or antigen-binding fragment thereof downregulates delta 1 positive and delta 2 positive and delta 3 positive gamma delta TCRs 20 In some embodiments of this aspect, the antibody or antigen-binding fragment thereof selectively activates and / or induces proliferation of delta 1 positive and delta 2 positive and delta 3 positive gamma delta cells. 25 Clone 567 (CYTA013): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at 30 least 99% or 100% identity to SEQ ID NO: 224; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 225; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 226; and / or a light chain variable region comprising: 5 a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 227; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at 10 least 99% or 100% identity to SEQ ID NO: 228; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 229. 15 In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 224, 225 and 226, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 227, 228 and 229, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 20 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 118 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 119, such that any sequence variations occur outside the CDR regions. 25 In this aspect the antibody or antigen-binding fragment thereof may a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 118 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity 30 to SEQ ID NO: 119. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 118 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 119. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino 5 acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the 10 antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light 15 chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 353 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, 20 at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 354. Any sequence variation may occur outside the CDR regions or outside the VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 353 and SEQ ID NO: 354. 25 Clone 578 (CYTA014): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at 30 least 99% or 100% identity to SEQ ID NO: 230; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 231; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 232; and / or a light chain variable region comprising: 5 a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 233; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at 10 least 99% or 100% identity to SEQ ID NO: 234; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 235. 15 In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 230, 231 and 232, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 233, 234 and 235, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 20 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 120 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 121, such that any sequence variations occur outside the CDR regions. 25 In this aspect the antibody or antigen-binding fragment thereof may a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 120 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity 30 to SEQ ID NO: 121. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 120 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 121. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino 5 acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the 10 antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light 15 chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 355 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, 20 at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 356. Any sequence variation may occur outside the CDR regions or outside the VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 355 and SEQ ID NO: 356. 25 In some embodiments of this aspect, the antibody or antigen-binding fragment thereof specifically binds to human TRGC2 / TRDC heterodimeric constant domain antigen and specifically binds to human TRGC1 / TRDC heterodimeric constant domain antigen. In some embodiments of this aspect, the antibody or antigen-binding fragment thereof specifically 30 binds to human TRGC2 / TRDC heterodimeric constant domain antigen, specifically binds to human TRGC1 / TRDC heterodimeric constant domain antigen and specifically binds to cynomolgus TRGC / TRDC heterodimeric constant domain antigen. In some embodiments of this aspect, the antibody or antigen-binding fragment thereof promotes gamma delta T cell mediated killing (optionally THP-1 cell killing in co-culture assay). In some embodiments of this aspect, the antibody or antigen-binding fragment thereof binds to PEER 5 cells expressing TRGC2 positive TCRs. In some embodiments of this aspect, the antibody or antigen-binding fragment thereof specifically binds to delta 1 positive and delta 2 positive and delta 3 positive gamma delta TCRs. 10 In some embodiments of this aspect, the antibody or antigen-binding fragment thereof downregulates delta 1 positive and delta 2 positive and delta 3 positive gamma delta TCRs In some embodiments of this aspect, the antibody or antigen-binding fragment thereof selectively activates and / or induces proliferation of delta 1 positive and delta 2 positive and delta 3 positive 15 gamma delta cells. Clone 641 (CYTA015): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising a heavy chain variable region comprising: 20 a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 236; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at 25 least 99% or 100% identity to SEQ ID NO: 237; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 238; and / or a light chain variable region comprising: 30 a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 239; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 240; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 241. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 236, 237 and 238, respectively, and 10 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 239, 240 and 241, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 122 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 15 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 123, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at 20 least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 122 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 123. 25 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 122 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 123. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant 30 domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 10 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 357 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 358. Any sequence variation may occur outside the CDR regions or outside the 15 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 357 and SEQ ID NO: 358. Clone 676 (CYTA016): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 20 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 242; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 25 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 243; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 244; and / or 30 a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 245; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 246; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 247. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 242, 243 and 244, respectively, and 10 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 245, 246 and 247, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 124 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 15 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 125, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 20 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 124 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 125. 25 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 124 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 125. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant 30 domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 10 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 359 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 360. Any sequence variation may occur outside the CDR regions or outside the 15 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 359 and SEQ ID NO: 360. Clone 680 (CYTA017): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 20 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 248; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 25 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 249; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 250; and / or 30 a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 251; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 252; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 253. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 248, 249 and 250, respectively, and 10 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 251, 252 and 253, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 126 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 15 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 127, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 20 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 126 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 127. 25 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 126 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 127. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant 30 domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 10 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 361 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 362. Any sequence variation may occur outside the CDR regions or outside the 15 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 361 and SEQ ID NO: 362. Clone 697 (CYTA018): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 20 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 254; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 25 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 255; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 256; and / or 30 a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 257; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 258; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 259. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 254, 255 and 256, respectively, and 10 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 257, 258 and 259, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 128 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 15 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 129, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 20 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 128 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 129. 25 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 128 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 129. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant 30 domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 10 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 363 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 364. Any sequence variation may occur outside the CDR regions or outside the 15 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 363 and SEQ ID NO: 364. Clone 717 (CYTA019): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 20 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 260; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 25 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 261; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 262; and / or 30 a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 263; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 264; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 265. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 260, 261 and 262, respectively, and 10 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 263, 264 and 265, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 130 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 15 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 131, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 20 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 130 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 131. 25 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 130 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 131. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant 30 domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 10 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 365 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 366. Any sequence variation may occur outside the CDR regions or outside the 15 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 365 and SEQ ID NO: 366. Clone 731 (CYTA020): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 20 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 266; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 25 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 267; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 268; and / or 30 a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 269; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 270; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 271. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 266, 267 and 268, respectively, and 10 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 269, 270 and 271, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 132 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 15 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 133, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 20 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 132 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 133. 25 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 132 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 133. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant 30 domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 10 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 367 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 368. Any sequence variation may occur outside the CDR regions or outside the 15 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 367 and SEQ ID NO: 368. Clone 734 (CYTA021): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 20 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 272; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 25 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 273; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 274; and / or 30 a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 275; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 276; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 277. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 272, 273 and 274, respectively, and 10 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 275, 276 and 277, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 134 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 15 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 135, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 20 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 134 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 135. 25 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 134 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 135. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant 30 domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 10 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 369 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 370. Any sequence variation may occur outside the CDR regions or outside the 15 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 369 and SEQ ID NO: 370. Clone 745 (CYTA022): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 20 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 278; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 25 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 279; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 280; and / or 30 a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 281; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 282; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 283. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 278, 279 and 280, respectively, and 10 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 281, 282 and 283, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 136 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 15 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 137, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 20 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 136 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 137. 25 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 136 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 137. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant 30 domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 10 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 371 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 372. Any sequence variation may occur outside the CDR regions or outside the 15 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 371 and SEQ ID NO: 372. Clone 759 (CYTA023): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 20 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 284; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 25 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 285; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 286; and / or 30 a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 287; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 288; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 289. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 284, 285 and 286, respectively, and 10 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 287, 288 and 289, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 138 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 15 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 139, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 20 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 138 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 139. 25 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 138 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 139. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant 30 domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 10 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 373 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 374. Any sequence variation may occur outside the CDR regions or outside the 15 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 373 and SEQ ID NO: 374. Clone 811 (CYTA024): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 20 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 290; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 25 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 291; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 292; and / or 30 a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 293; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 294; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 295. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 290, 291 and 292, respectively, and 10 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 293, 294 and 295, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 140 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 15 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 141, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 20 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 140 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 141. 25 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 140 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 141. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant 30 domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 10 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 375 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 376. Any sequence variation may occur outside the CDR regions or outside the 15 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 375 and SEQ ID NO: 376. Clone 894 (CYTA025): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 20 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 296; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 25 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 297; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 298; and / or 30 a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 299; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 300; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 301. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 296, 297 and 298, respectively, and 10 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 299, 300 and 301, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 142 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 15 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 143, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 20 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 142 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 143. 25 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 142 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 143. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant 30 domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 10 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 377 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 378. Any sequence variation may occur outside the CDR regions or outside the 15 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 377 and SEQ ID NO: 378. Clone 953 (CYTA026): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 20 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 302; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 25 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 303; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 304; and / or 30 a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 305; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 306; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 307. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 302, 303 and 304, respectively, and 10 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 305, 306 and 307, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 144 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 15 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 145, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 20 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 144 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 145. 25 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 144 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 145. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant 30 domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 10 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 379 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 380. Any sequence variation may occur outside the CDR regions or outside the 15 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 379 and SEQ ID NO: 380. Clone 957 (CYTA027): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 20 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 308; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 25 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 309; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 310; and / or 30 a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 311; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 312; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 313. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 308, 309 and 310, respectively, and 10 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 311, 312 and 313. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 146 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at 15 least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 147, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 20 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 146 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 147. 25 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 146 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 147. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant 30 domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 10 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 381 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 382. Any sequence variation may occur outside the CDR regions or outside the 15 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 381 and SEQ ID NO: 382. Clone 1125 (CYTA028): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 20 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 314; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 25 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 315; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 316; and / or 30 a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 317; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 318; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 319. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 314, 315 and 316, respectively, and 10 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 317, 318 and 319, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 148 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 15 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 149, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 20 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 148 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 149. 25 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 148 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 149. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant 30 domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 10 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 383 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 384. Any sequence variation may occur outside the CDR regions or outside the 15 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 383 and SEQ ID NO: 384. Clone 1171 (CYTA029): In one aspect of the invention an antibody or antigen-binding fragment thereof is provided, comprising 20 a heavy chain variable region comprising: a VHCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 320; a VHCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 25 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 321; and a VHCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 322; and / or 30 a light chain variable region comprising: a VLCDR1 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 323; a VLCDR2 comprising or consisting of an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 324; and a VLCDR3 comprising or consisting of an amino acid sequence having at least 90%, at least 5 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a SEQ ID NO: 325. In this aspect the antibody or antigen-binding fragment thereof may comprise a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 320, 321 and 322, respectively, and 10 a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 323, 324 and 325, respectively. The antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 150 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at 15 least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 151, such that any sequence variations occur outside the CDR regions. In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 20 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 150 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 151. 25 In this aspect the antibody or antigen-binding fragment thereof may comprise a VH comprising or consisting of the amino acid sequence of SEQ ID NO: 150 and a VL comprising or consisting of the amino acid sequence of SEQ ID NO: 151. In this aspect the antibody or antigen-binding fragment thereof may comprise a heavy chain constant 30 domain and a light chain constant domain. The heavy chain constant domain may be an IGHG1 human heavy chain constant domain. The heavy chain constant domain may comprise or consist of the amino acid sequence of SEQ ID NO: 326. In this aspect the antibody or antigen-binding fragment thereof may comprise a light chain constant domain. The light chain constant domain may be either a kappa (IGKC human) or a lambda (IGLC1 human) constant domain. The light chain constant domain may comprise or consist of the amino acid sequence SEQ ID NO: 327 or 328. The heavy chain constant domain may be paired with either a kappa or a lambda light chain constant domain so the constant domains of the antibody or antigen-binding fragment thereof may comprise SEQ ID NO: 326 and SEQ ID NO: 327 or SEQ ID NO: 326 and SEQ ID NO: 328. 5 In this aspect the antibody or antigen-binding fragment thereof may comprise a full length heavy chain comprising a heavy chain variable region and a heavy chain constant region and / or a full length light chain comprising a light chain variable region and a light chain constant region. The antibody or antigen-binding fragment thereof may comprise an amino acid sequence having at least 70%, at least 10 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 385 and / or an amino acid sequence having at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 386. Any sequence variation may occur outside the CDR regions or outside the 15 VH or VL regions. In one embodiment the antibody or antigen-binding fragment thereof may comprise the amino acid sequences of SEQ ID NO: 385 and SEQ ID NO: 386. Uses of antibodies of the invention Medicaments for modulating gamma delta T cells 20 The antibodies or antigen-binding fragments described herein may be useful for modulation of gamma delta T cells in a patient. In one aspect the antibodies or antigen-binding fragments described herein are therefore comprised in medicaments for such purposes. The term “modulation” may include some or all of the following: 25 ^ stimulating gamma delta T cells, e.g. increasing the potency of gamma delta cells; ^ degranulation of gamma delta T cells; ^ expansion of gamma delta T cells, e.g. by increasing the numbers of gamma delta T cells or stopping depletion of gamma delta T cells ^ increasing persistence of gamma delta T cells, e.g. by preventing exhaustion; 30 ^ causing, promoting or increasing gamma delta T cell mediated killing; ^ activation of gamma delta T cells e.g. downregulation of TCR / CD3 complex due to internalisation In one embodiment, the invention provides a method of activating at least one gamma delta T cell in a subject, comprising the step of administering an antibody or antigen-binding fragment thereof as defined herein. In one embodiment, the invention provides a method of causing or increasing proliferation of gamma delta T cells in a subject, comprising the step of administering to the subject 5 an antibody or antigen-binding fragment thereof as defined herein. In one embodiment, the invention is a method of causing or increasing gamma delta T cell degranulation in a subject, comprising the step of administering to the subject an antibody or antigen-binding fragment thereof as defined herein. In one embodiment, the invention provides a method of causing or increasing gamma delta T cell mobilization in a subject, comprising the step of administering to the subject an antibody or antigen- 10 binding fragment thereof as defined herein. In one embodiment, the invention is a method of causing or increasing gamma delta T cell mediated killing activity (e.g. T cell mediated killing activity) in a subject, comprising the step of administering to the subject an antibody or antigen-binding fragment thereof as defined herein. In one embodiment, the invention is a method of or increasing resistance to exhaustion of gamma delta T cells in a subject, comprising the step of administering to the subject 15 an antibody or antigen-binding fragment thereof as defined herein. In one embodiment, the invention is a method of increasing survival of gamma delta T cells in a subject, comprising the step of administering to the subject an antibody or antigen-binding fragment thereof as defined herein. In one embodiment, the invention is a method of causing or increasing gamma delta T cytotoxicity in a subject, comprising the step of administering to the subject an antibody or antigen-binding fragment 20 thereof as defined herein. According to a further aspect of the invention, there is provided a method of stimulating an immune response in a subject, the method comprising administration to the subject an antibody or antigen- binding fragment thereof in an amount effective at stimulating an immune response. An “immune 25 response” is a measurable change in at least one cell, or one cell-type, or one endocrine pathway, or one exocrine pathway, of the immune system (including but not limited to a cell-mediated response, a humoral response, a cytokine response, a chemokine response) upon addition of a modulating antibody. 30 Importantly, the antibody-based medicaments of the invention are capable of selectively targeting multiple sub-classes of gamma delta cells and they can therefore modulate all sub-classes of gamma delta T cells. Methods of treatment As disclosed herein, the antibodies of the invention are useful as medicaments. Therefore in one aspect of the invention there is provided an antibody or antigen-binding fragment thereof as defined herein for use as a medicament. 5 In one aspect of the invention there is provided an antibody or antigen-binding fragment thereof as defined in any other aspect, or the pharmaceutical composition or kit as defined in any other aspect for use in a method of treating a disease or disorder in a subject, optionally wherein the disease is cancer. 10 In one embodiment, the invention is a method of treating a disease or disorder in a subject in need thereof, comprising the step of administering the antibody or antigen-binding fragment thereof as defined herein to the subject. In one embodiment, the disease or disorder is cancer. In one embodiment, the antibody or antigen-binding fragment thereof is for use in a method of treating cancer. 15 References to “subject”, “patient” or “individual” refer to a subject, in particular a mammalian subject, to be treated. Mammalian subjects include humans, non-human primates, farm animals (such as cows), sports animals, or pet animals, such as dogs, cats, guinea pigs, rabbits, rats or mice. In preferred embodiments, the subject is a human. In alternative embodiments, the subject is a non-human 20 mammal, such as a mouse. As used herein, “treating a disease or disorder” means reducing the frequency and / or severity of at least one sign or symptom of the disease or disorder experienced by a subject when compared to an earlier time point, for example before the antibody is administered. According to a further aspect of the invention, there is provided the composition, pharmaceutical 25 composition or kit as defined herein for use as a medicament. In one embodiment, the pharmaceutical composition or kit is for use in a method of treating of a disease or disorder. In a further embodiment, the pharmaceutical composition or kit is for use a method of treating of cancer. According to further aspects of the invention, there is provided the use of an antibody or antigen- 30 binding fragment thereof as defined herein for the manufacture of a medicament, for example in the treatment of cancer. In one embodiment, the antibody or antigen-binding fragment thereof is administered to a subject, wherein the subject has a disease or disorder such as cancer. According to a further aspect of the invention, there is provided the pharmaceutical composition as defined herein for use as a medicament. In one embodiment, the pharmaceutical composition is administered to a subject, wherein the subject has a disease or disorder such as cancer. 5 In various embodiments, the cancer that can be treated by the disclosed methods and compositions include, but are not limited to acute lymphoblastic, acute myeloid leukemia, adrenocortical carcinoma, appendix cancer, basal cell carcinoma, bile duct cancer, bladder cancer, bone cancer, osteosarcoma and malignant fibrous histiocytoma, brain stem glioma, brain tumor, brain tumor, brain stem glioma, 10 central nervous system atypical teratoid / rhabdoid tumor, central nervous system embryonal tumors, cerebellar astrocytoma, cerebral astrocytoma / malignant glioma, craniopharyngioma, ependymoblastoma, ependymoma, medulloblastoma, medulloepithelioma, pineal parenchymal tumors of intermediate differentiation, supratentorial primitive neuroectodermal tumors and pineoblastoma, visual pathway and hypothalamic glioma, brain and spinal cord tumors, breast cancer, 15 bronchial tumors, Burkitt lymphoma, carcinoid tumor, gastrointestinal carcinoid tumor, central nervous system atypical teratoid / rhabdoid tumor, central nervous system embryonal tumors, central nervous system lymphoma, cerebellar astrocytoma cerebral astrocytoma / malignant glioma, cervical cancer, chordoma, chronic lymphocytic leukemia, chronic myelogenous leukemia, chronic myeloproliferative disorders, colon cancer, colorectal cancer, craniopharyngioma, cutaneous T cell 20 lymphoma, esophageal cancer, Ewing family of tumors, extragonadal germ cell tumor, extrahepatic bile duct cancer, intraocular melanoma, retinoblastoma, gallbladder cancer, gastric (stomach) cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (gist), germ cell tumor, gestational trophoblastic tumor, glioma, glioma brain stem, glioma cerebral astrocytoma, glioma visual pathway and hypothalamic, hairy cell leukemia, head and neck cancer, hepatocellular (liver) cancer, Langerhans 25 cell histiocytosis, Hodgkin lymphoma, hypopharyngeal cancer, hypothalamic and visual pathway glioma, intraocular melanoma, islet cell tumors, kidney (renal cell) cancer, Langerhans cell histiocytosis, laryngeal cancer, acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, hairy cell leukemia, lip and oral cavity cancer, liver cancer, non-small cell lung cancer, small cell lung cancer, aids-related lymphoma, Burkitt 30 lymphoma, cutaneous T cell lymphoma, non-Hodgkin lymphoma, primary central nervous system lymphoma, Waldenstrom macroglobulinemia, malignant fibrous histiocvtoma of bone and osteosarcoma, medulloblastoma, melanoma, Merkel cell carcinoma, mesothelioma, metastatic squamous neck cancer with occult primary, mouth cancer, multiple endocrine neoplasia syndrome, multiple myeloma / plasma cell neoplasm, mycosis, fungoides, myelodysplastic syndromes, myelodysplastic / myeloproliferative diseases, myelogenous leukemia, myeloid leukemia, myeloid leukemia acute, multiple myeloma, myeloproliferative disorders, nasal cavity and paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, non-small cell lung cancer, oral cancer, oral cavity cancer, oropharyngeal cancer, osteosarcoma and malignant fibrous histiocytoma of bone, ovarian 5 cancer, ovarian epithelial cancer, ovarian germ cell tumor, ovarian low malignant potential tumor, pancreatic cancer, pancreatic cancer, papillomatosis, parathyroid cancer, penile cancer, pharyngeal cancer, pheochromocytoma, pineal parenchymal tumors of intermediate differentiation, pineoblastoma and supratentorial primitive neuroectodermal tumors, pituitary tumor, plasma celt neoplasm / multiple myeloma, pleuropulmonary blastoma, primary central nervous system lymphoma, 10 prostate cancer, rectal cancer, renal cell (kidney) cancer, renal pelvis and ureter, respiratory tract carcinoma involving the nut gene on chromosome 15, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, sarcoma, Ewing family of tumors, Kaposi sarcoma, soft tissue sarcoma, uterine sarcoma, Sezary syndrome, skin cancer (nonmelanoma), skin cancer (melanoma), Merkel cell skin carcinoma, small cell lung cancer, small intestine cancer, soft tissue sarcoma, squamous cell carcinoma, squamous 15 neck cancer, stomach (gastric) cancer, supratentorial primitive neuroectodermal tumors, T cell lymphoma, testicular cancer, throat cancer, thymoma and thymic carcinoma, thyroid cancer, transitional cell cancer of the renal pelvis and ureter, gestational trophoblastic tumor, urethral cancer, uterine cancer, uterine sarcoma, vaginal cancer, vulvar cancer, Waldenstrom macroglobulinemia, and Wilms tumor. 20 Other uses Use of Anti TRDC, TRGC1 or TRGC2 Antibodies to identify a gamma delta cell or confirm the identity of a gamma delta cell as GC1 and / or GC2 positive 25 Antibodies of the invention, specifically anti TRDC, TRGC1 or TRGC2 antibodies may be used to confirm the identity of a gamma delta cell or cells as GC1 and / or GC2 positive. This may be useful to determine whether a specific patient or sample may react to different antibody medicaments depending on the levels of GC1 or GC2 positive gamma delta cells in the patient or sample. For example, a patient or sample with a high level of GC1 positive cells compared with the level of GC2 cells may be treated 30 more efficiently with a GC1 specific antibody than with a GC2 specific antibody (or vice versa). This may also be useful for obtaining purified or enriched populations of GC1 or GC2 positive gamma delta cells. See also Example 13. A method of determining whether a gamma delta cell is GC1 and / or GC2 positive is therefore provided, which utilises antibodies of the invention which specifically bind to human TRDC, human TRGC1 and / or human TRGC2 antigen expressed on the surface of said cells. 5 A method of determining whether a gamma delta cell is GC1 positive or GC2 positive, the method comprising: a) providing a population of cells comprising gamma delta cells; b) contacting the cells with an anti-GC1 antibody of the invention or an anti-GC2 antibody of the invention; 10 c) identifying, selecting, confirming or characterizing the cells that have been specifically bound by the anti-GC1 antibody or the anti-GC2 antibody to identify whether a gamma delta cell is GC1 positive or GC2 positive. The population of cells may be a population of immune cells comprising or consisting of gamma delta 15 cells. The cells may be human cells or cynomolgus cells. The cells may be provided as a blood sample extract, processed blood sample extract, tissue sample or processed tissue sample. The gamma delta cells will express gdTCR receptor complex on the cell surface. In some embodiments, the gdTCR is complexed with as a gamma delta TCR / CD3 complex and presented on the surface of a human or cynomolgus cell. 20 When an anti-GC1 antibody of the invention is used in the method, it specifically binds to TRGC1 antigen expressed on the surface of GC1 positive gamma delta cells. The anti-GC1 antibody may be specific for TRGC1 and not TRGC2 and thus are able to preferentially bind to and confirm the identity human TRGC1 antigen expressing cells. In some embodiments the anti-GC1 antibodies employed in 25 such methods are characterized in that they are 2-fold; or 5-fold; or 10-fold; or 50-fold; or 100-fold; or 500-fold; or 1000-fold more specific for TRGC1 antigen than TRGC2 antigen when measured under the same or substantially the same conditions. In some embodiments the anti-GC1 antibodies employed in such methods are characterized in that they are 10-fold more specific for TRGC1 antigen than TRGC2 antigen when measured under the same or substantially the same conditions. A gamma delta cell that 30 expresses TCR comprising TRGC1 will be specifically bound by an anti-GC1 antibody of the invention and can be identified as a GC1 positive gamma delta cell. When an anti-GC2 antibody of the invention is used in the method, it specifically binds to TRGC2 antigen expressed on the surface of GC2 positive gamma delta cells. The anti-GC2 antibody may be specific for TRGC2 and not TRGC1 and thus are able to preferentially bind to and confirm the identity human TRGC2 antigen expressing cells. In some embodiments the anti-GC2 antibodies employed in such methods are characterized in that they are 2-fold; or 5-fold; or 10-fold; or 50-fold; or 100-fold; or 500-fold; or 1000-fold more specific for TRGC2 antigen than TRGC1 antigen when measured under the 5 same or substantially the same conditions. In some embodiments the anti-GC2 antibodies employed in such methods are characterized in that they 10-fold more specific for TRGC2 antigen than TRGC1 antigen when measured under the same or substantially the same conditions. A gamma delta cell that expresses TCR comprising TRGC2 will be specifically bound by an anti-GC2 antibody of the invention and can be identified as a GC2 positive gamma delta cell. 10 The step of selecting the cells that have been specifically bound by the anti-GC1 antibody or the anti- GC2 antibody to identify whether a gamma delta cell is GC1 positive or GC2 positive may be via direct or indirect detection methods. For example, the antibodies of the invention may be labelled, e.g. fluorescently labelled such that they can be detected using fluorescence imaging or other suitable 15 methods for detecting fluorescence labels. Chromogenic detection or physical detection methods such as biotinylation may also be used. The antibodies may also be detected using indirect methods wherein a second antibody that recognises the primary antibody is detected. In some embodiments, the method further comprises a step of: 20 d) enriching the population of cells for GC1 or GC2 positive cells, optionally using cell sorting. The method may employ any technique for cell detection or cell sorting known in the art. For example, the method may utilise immunohistochemistry (IHC) staining or flow-based methodologies such as fluorescence-activated cell sorting (FACS). 25 In some embodiments, the step of enriching (or sorting or purifying) the cells may employ standard flow-sorting methodology such as FACS to separate GC1 or GC2 positive cells from the general population of cells. A method of obtaining a purified or enriched population of GC1 positive gamma delta T cells is therefore provided, using the anti-TRGC1 antibodies of the invention. A method of 30 obtaining a purified or enriched population of GC2 positive gamma delta T cells is therefore provided, using the anti-TRGC2 antibodies of the invention. This method can also be applied to anti-TRDC antibodies of the invention. Since all gamma delta cells (regardless of their variable domain or GC1 / GC2 domain) comprise a constant delta region (TRDC) the method can be applied when it is advantageous to identify, select for, purify or enrich for all gamma delta cells in a population. A method of identifying a gamma delta cell is therefore provided, the method comprising: 5 a) providing a population of cells; b) contacting the cells with an anti-TRDC antibody of the invention c) identifying, selecting, confirming or characterizing the cells that have been specifically bound by the anti-TRDC antibody to identify whether a cell expresses a gamma delta TCR. 10 An advantage of this method is that any cell that expresses a gamma delta TCR will be identified, regardless of how it is classified by its variable region (e.g. Vδ1 etc) and regardless of which gamma constant region the TCR comprises (GC1 / GC2). It is therefore not required to have previously characterised a cell population to determine the subtype of the gamma delta cells in order to identify, select, purify or enrich for said cells. Antibodies that have been shown to bind only to the TRDC and 15 not the variable regions or the TRGC1 / TRGC2 are therefore useful in this method. Use of TRDC, TRGC1 and TRGC2 domains as biomarkers epitope and antibodies which recognize them Determining whether a patient or group of patients may respond to a particular antibody medicament 20 can be challenging. Finding a relevant biomarker is therefore important, as is finding a reliable method to identify and monitor said biomarker. This is especially pertinent when the cells on which an antibody medicament acts are inaccessible, scarce, or hard to assay (such as Vδ1 and Vδ3 cells, which are typically tissue resident and hard to access without a tissue biopsy). However this is also a challenge when the cell type or epitope to be targeted includes a broad class of target, and the use of multiple 25 biomarkers should be avoided. For example, if medicament acts on gamma delta cells generally, regardless of subtype, a biomarker is required that is not limited to subtype, but is a biomarker for all gamma delta cells. A constant domain present on all gamma delta TCR cells may be used as a biomarker for patient treatment decision making and / or patient selection or stratification. 30 A method of determining whether a patient is a suitable recipient of an anti-gamma delta antibody medicament is provided, wherein the method comprises: a) measuring the level of a constant domain biomarker (TRDC, TRGC1 or TRGC2) in a blood sample that has been obtained from a patient; b) determining the level of this biomarker is above a suitable threshold; c) treating the patient (or recommending the patient for treatment) with an antibody medicament which binds the constant domain of a gamma delta TCR positive immune cell. As used herein, the term “marker” or “biomarker” refers to an antigen, or a fragment of antigen, the 5 change in amount and / or the detection of which can be correlated with a particular physical condition or state. Particular biomarkers used in the present invention are correlated with the response of a patient to an anti-gamma delta antibody, and are also used in the methods described herein. For example, a constant domain biomarker may be a gamma delta TCR, which comprises a constant domain. The detection and / or quantification of such markers time may be achieved by any means 10 known in the art. In one embodiment, the constant domain biomarker is TRGC1 or TRGC2 or TRDC. As used herein, the term “amount” or “level” refers to a quantity of a marker epitope in a biological sample and / or control or reference sample. The quantity of a marker can be, for example, a quantity present on the surface of a cell as recoded by flow analysis. This may be reported as % of cells positive 15 for the marker epitope, or expression levels or mean expression levels of a marker epitope present on a cell. The term can alternatively include combinations thereof. The amount or level of the marker may refer to the absolute amount or level of the marker. Alternatively, a change in the relative level or amount of marker may be assessed by comparing the level or amount of the epitope in a sample from the subject with a control value or reference value. Alternatively, the relative amount or level of the 20 marker may in some instances refer to the quantity or level of the marker relative to the quantity or level of marker in the sample at another point in time. The level of biomarker may be detected by any suitable means, for example by detection using any of the antibodies disclosed herein. The “threshold” is a level of biomarker that can be determined by the skilled person as being indicative of a particular feature. In this example, the threshold may be a % of cells positive for the marker epitope above which 25 an antibody medicament would be expected or is known to be effective. A skilled person would be able to determine and adjust a threshold based on a specific patient, their history, clinical state and the antibody medicament that is being considered for administration. In some embodiments, the suitable threshold is one in which a population is separated by a cut-off value which divides the population into two subsets wherein the treatment is considered to be more effective in one of these 30 subsets. Typically this 'positive' subset is as large as possible. Such a cut-of value may be a relative value. For example, greater than 5% CD3 positive cells are also GC1 positive cells. The constant domain biomarker will be expressed as part of a TCR expressed on the surface or a gamma delta cell, likely a Vδ2+ gamma delta cell, present in the blood sample obtained from the patient. 5 The disease or disorder the patient is being treated or recommended for treatment for may be cancer. In some embodiments the cancer may be a blood cancer or a non-blood cancer such as a solid tumor or tissue cancer. In cases where the cancer is a non-blood cancer, the method utilises antibodies that recognize the human TRDC or TRGC domain present in tissue resident delta one TCR positive cells and tissue-resident delta three TCR positive cells, and which also recognizes said same domain also present 10 on delta two TCR positive cells more prevalent in blood and wherein the levels of blood resident delta two cells are analysed to inform target engagement by said medicament and without the need for a tissue biopsy. If it is determined that the level of constant domain biomarker is above a suitable threshold, the 15 patient is deemed to be a suitable recipient of an anti-gamma delta antibody medicament, which in some embodiments is an anti-TRGC1 antibody, or an anti-TRGC2 antibody or an anti-TRDC antibody. In some embodiments, the antibody is any one of the antibodies disclosed herein. The patient is therefore treated by administration of said antibody, or is recommended for treatment by administration of said antibody. 20 The constant domain has therefore served as a biomarker to indicate the level of gamma delta cells present in the sample to enable a determination of whether an antibody medicament should be deployed. 25 The constant domain biomarkers can also be used to determine whether an existing treatment is effective and whether it should be continued or discontinued, or whether the dosage should be adjusted. A method of assessing a treatment regimen without a tissue biopsy is provided, the method 30 comprising a) administering an antibody of the invention (an anti-TRDC, an anti-TRGC1 or an anti-TRGC2 antibody) to a patient in need thereof; b) taking a sample of blood from the patient; c) analysing the Vδ2+ gamma delta cells in the blood sample to confirm the administered antibody has engaged with the gamma delta cells; d) using this analysis to inform the treatment regimen for the patient. 5 A method of assessing a treatment regimen without a tissue biopsy is provided, the method comprising a) providing a blood sample that has been obtained from a patient to whom an antibody of the invention (an anti-TRDC, an anti-TRGC1 or an anti-TRGC2 antibody) has been administered; b) analysing the Vδ2+ gamma delta cells in the blood sample to confirm the administered 10 antibody has engaged with the gamma delta cells; c) using this analysis to inform the treatment regimen for the patient. The antibody may be any antibody provided herein, and will bind specifically to TRDC or TRGC1 or TRGC2. In a preferred embodiment the antibody is a human antibody and binds specifically to human 15 TRDC or human TRGC1 or human TRGC2. The antibody of the invention may have been administered to the patient at least 12 hours, or at least 24 hours, or at least 48 hours, or at least 72 hours, or at least 144 hours before the blood sample was obtained. 20 The Vδ2+ gamma delta cells in the blood sample may be analysed by any suitable method known in the art. For example the antibodies that were administered to the patient may comprise a label or marker to enable them to be identified, such as a fluorescent marker. 25 The TRDC or TRGC1 or TRGC2 levels expressed on the delta two cells is considered a biomarker and levels present on the delta two cells from a blood sample derived from the patient are measured. In some embodiments, the biomarker comprising a TRDC or TRGC1 or TRGC2 epitope present on the delta-two positive blood cells are analysed pre- and post- administration of the antibody in order to 30 assess or demonstrate a change in phenotype or number of delta-two positive cells In some related embodiment, the results of the blood analysis for levels of the biomarker epitope comprising a TRDC or TRGC1 or TRGC2 present on the delta-two positive blood cells inform the patient selection criteria, and / or the timing, and / or the quantity of antibody to be dosed. In some embodiments the analysis of the biomarker comprising a TRDC or TRGC1 or TRGC2 epitope present on the delta-two positive blood cells is employed as a surrogate for the response to delta one and delta three cells also engaged by said antibody. 5 Use of Anti TRDC, TRGC1 or TRGC2 Antibodies as medicaments to induce the proliferation of gamma delta cells In one aspect, the anti-TRDC, anti-TRGC1 or anti-TRGC2 antibodies of the invention are useful in 10 methods of inducing the proliferation of delta one TCR positive cells, and delta two TCR positive cells, and delta three TCR positive cells. In some embodiments, the anti-TRDC, anti-TRGC1 or anti-TRGC2 antibodies of the invention induce a greater than 150-fold, 200-fold, 300-fold, 450-fold or 460-fold proliferation in the number of delta one 15 TCR positive cells, and delta two TCR positive cells, and delta three TCR positive cells. In some embodiments, the antibody or antigen-binding fragment thereof of the invention induces a greater than 150-fold, 200-fold, 300-fold, 450-fold or 460-fold proliferation in the number of delta three TCR positive cells. 20 In some embodiments, the antibodies are formulated as an antibody medicament suitable for administration to a patient. Upon administration of the antibody medicament to a patient there is observed a measurable increase in the numbers of delta-one TCR positive cells in vivo and / or delta two positive cells in vivo and / or delta three TCR positive cells in vivo as measured via a second blood sample taken from said patient after dosing, wherein said increase is significant relative to the numbers 25 of said cells measured in a first blood sample analyzed by the same method when said first blood sample was taken from the same patient prior to the aforementioned administration or dose of the antibody medicament. Use of Anti TRDC, TRGC1 or TRGC2 Antibodies as medicaments to induce the TCR downregulation of 30 gamma delta cells Gamma delta TCR downregulation is synonymous with receptor activation. However the challenges are measuring downregulation are hampered by the fact that the cells may become invisible. In one aspect, the anti-TRDC, anti-TRGC1 or anti-TRGC2 antibodies of the invention are useful in methods of inducing TCR downregulation of multiple gamma delta cell-types selected from a group of delta one TCR positive cells, delta two TCR positive cells, and delta three TCR positive cells. 5 In a related embodiment the TCR downregulation observed and / or measured in delta two positive cells present in blood correlates with the TCR downregulation also observed and / or measured in delta one positive cells or delta three positive cells that are only present in small quantities in blood. In a related embodiment the TCR downregulation induced upon contact of the antibody with the delta 10 one, delta two and / or delta three TCR positive cells present in blood or a processed blood sample derived from patient informs a physicians decision on a patient’s treatment regimen. Pharmaceutical compositions In one aspect of the invention, there is provided a composition comprising the antibody or antigen- 15 binding fragment thereof as defined herein. In such embodiments, the composition may comprise the antibody, optionally in combination with other excipients. Also included are compositions comprising one or more additional active agents (e.g. active agents suitable for treating the diseases mentioned herein). 20 In one aspect of the invention, there is provided a pharmaceutical composition comprising the antibody or antigen-binding fragment thereof as defined herein, together with a pharmaceutically acceptable diluent or carrier. The antibodies of the invention can be incorporated into pharmaceutical compositions suitable for administration to a subject. Typically, the pharmaceutical composition comprises an antibody of the invention and a pharmaceutically acceptable carrier. As used herein, 25 "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, buffers, salt solutions, stabiliser, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are physiologically compatible. Examples of pharmaceutically acceptable carriers include one or more of water, saline, salts, phosphate buffered saline, dextrose, glycerol, ethanol and the like, as well as combinations thereof. In many cases, it will be preferable to include 30 isotonic agents, for example, sugars, polyalcohols such as mannitol, sorbitol, or sodium chloride in the composition. Pharmaceutically acceptable substances such as wetting or minor amounts of auxiliary substances such as wetting or emulsifying agents, preservatives or buffers, which enhance the shelf life or effectiveness of the antibody or fragment thereof. The compositions of this invention may be in a variety of forms. These include, for example, liquid, semi-solid and solid dosage forms, such as liquid solutions (e.g. injectable and infusible solutions), dispersions or suspensions, tablets, pills, powders, liposomes and suppositories. The preferred form depends on the intended mode of administration and therapeutic application. Typical preferred 5 compositions are in the form of injectable or infusible solutions. The preferred mode of administration is parenteral (e.g. intravenous, subcutaneous, intraperitoneal, intramuscular, intrathecal). In a preferred embodiment, the antibody is administered by intravenous infusion or injection. In another preferred embodiment, the antibody is administered by intramuscular 10 or subcutaneous injection. Therapeutic compositions typically must be sterile and stable under the conditions of manufacture and storage. The composition can be formulated as a solution, microemulsion, dispersion, liposome, or other ordered structure suitable to high drug concentration. 15 It is within the scope of the invention to use the pharmaceutical composition of the invention in therapeutic methods for the treatment of diseases as described herein as an adjunct to, or in conjunction with, other established therapies normally used in the treatment of such diseases. 20 In a further aspect of the invention, the antibody, composition or pharmaceutical composition is administered sequentially, simultaneously or separately with at least one active agent. The pharmaceutical compositions of the invention may be formulated to include one or more additional pharmaceutically or therapeutically active components. The antibodies or antigen-binding 25 fragments thereof of the invention may be provided as part of a kit. Such kits may include instructions for use and / or additional pharmaceutically active components and / or additional therapeutically active agents. The antibodies or antigen-binding fragments and the additional pharmaceutically active components may be disposed separately within the kit, or in some embodiments the antibodies or antigen-binding fragments and the additional pharmaceutically active components may be formulated 30 together. Antibody Expression In one aspect of the invention there is provided a nucleic acid encoding the antibody or antigen-binding fragment of any other aspect of the invention. To express the antibodies, or antigen-binding fragments thereof, nucleic acids encoding partial or full- length light and heavy chains, as described herein, are inserted into expression vectors such that the genes are operatively linked to transcriptional and translational control sequences. Therefore, in one 5 aspect of the invention there is provided a vector (expression vector) comprising a nucleic acid as defined in as described in any other aspect or embodiment. Expression vectors include, for example, plasmids, retroviruses, cosmids, yeast artificial chromosomes (YACs) and Epstein-Barr virus (EBV) derived episomes. This may be a mammalian expression vector such used to express the antibody or antigen-binding fragment thereof in CHO or HEK293. Such vectors may be used in pairs, suitable 10 pairing the heavy and light chain variable sequences according to the pairing of various amino acid sequences providing the antibodies of the invention disclosed herein. Nucleic acids encoding the VH and VL regions can be inserted into separate vectors, alternatively sequences encoding both regions are inserted into the same expression vector. The nucleic acid(s) are inserted into the expression vector by standard methods (e.g. ligation of complementary restriction sites on the polynucleotide and15 vector, or blunt end ligation if no restriction sites are present). To express the antibodies or antigen- binding fragments thereof, nucleic acids encoding partial or full-length light and heavy chains, as described herein, are inserted into expression vectors such that the genes are operatively linked to transcriptional and translational control sequences. Therefore, in one embodiment, the expression vector comprises DNA encoding a VH region of any one of the VH SEQ ID NO disclosed in Table 3. In 20 another embodiment, the expression vector comprises DNA encoding a VL region of any one of the VL SEQ ID NO disclosed in Table 3. The present invention therefore provides nucleic sequences and expression vectors encoding all of the antibody sequences disclosed herein, including any variant antibody sequences disclosed herein 25 optionally comprising one or more amino acid substitutions. The nucleic and expression vectors of th...

Claims

1. CLAIMS 1. An antibody or antigen-binding fragment thereof that specifically binds human TRGC2 / TRDC heterodimeric constant domain antigen or a fragment thereof, wherein the antibody or antigen-binding fragment thereof is a human antibody or antigen-binding fragment thereof.

2. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen- binding fragment thereof also specifically binds: a. TRGC1 / TRDC heterodimeric constant domain antigen or a fragment thereof, optionally human TRGC1 / TRDC heterodimeric constant domain antigen.

3. The antibody or antigen-binding fragment thereof of any previous claim, wherein the antibody also specifically binds to the corresponding cynomolgus constant domain antigen (cyno TRGC / TRDC) or fragment thereof.

4. The antibody or antigen-binding fragment thereof of any previous claim, wherein the constant domain specifically bound by the antibody or antigen-binding fragment thereof comprises or consists of the amino acid sequence of any one of SEQ ID NOs: 1 to 9.

5. The antibody or antigen-binding fragment thereof of any previous claim, wherein the constant domain or fragment thereof specifically bound by the antibody or antigen-binding fragment thereof comprises an amino acid sequence that is at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or is 100% identical to any one of SEQ ID NOs: 10 to 20.

6. The antibody or antigen-binding fragment thereof of any previous claim, which does not specifically bind to a variable domain of a gamma delta T-cell receptor (gdTCR) or a fragment or fragments thereof.

7. The antibody or antigen-binding fragment thereof of any previous claim, wherein the constant domain fragment specifically bound by the antibody or antigen-binding fragment thereof comprises an Ig-like domain wherein the Ig-like domain comprises or consists of: (a) the canonical beta strands defined by residues 1 to 110 of SEQ ID NO: 1; (b) the canonical beta strands defined by residues 5 to 105 of SEQ ID NO: 2 (optionally residues 5 to 121); (c) the canonical beta strands defined by residues 5 to 105 of SEQ ID NO: 3; (d) residues 11 to 105 of SEQ ID NO: 3; or (e) residues 11 to 105 of SEQ ID NO:

2.

8. The antibody or antigen-binding fragment thereof of any previous claim, wherein the antibody or antigen-binding fragment thereof binds to immortalized cells expressing TRGC2 positive TCRs (for example PEER cells expressing TRGC2 positive TCRs).

9. The antibody or antigen-binding fragment thereof of any previous claim, comprising: a. a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 164, 165 and 166, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 167, 168 and 169, respectively; b. a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 200, 201 and 202, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 203, 204 and 205, respectively; c. a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 218, 219 and 220, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 221, 222 and 223, respectively; d. a VHCDR1, a VHCDR2 and a VHCDR3 comprising the amino acid sequences of SEQ ID NO: 230, 231 and 232, respectively, and a VLCDR1, a VLCDR2 and a VLCDR3 comprising the amino acid sequences of SEQ ID NOs: 233, 234 and 235, respectively.

10. The antibody or antigen-binding fragment thereof of any previous claim, wherein the antibody or antigen-binding fragment thereof does not comprise a cysteine residue in any of VHCDR1, VHCDR2, VHCDR3, VLCDR1, VLCDR2 and VLCDR3.

11. The antibody or antigen-binding fragment thereof of any previous claim, comprising: a. a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 98 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 99; b. a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 110 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 111; c. a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 116 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, atleast 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 117; d. a VH comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO: 120 and a VL comprising an amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO:

121.

12. The antibody or antigen-binding fragment thereof of any of claims 9-11, further comprising a heavy chain constant domain and a light chain constant domain, wherein the heavy chain constant domain comprises or consists of the amino acid sequence of SEQ ID NO: 326 or 389 and the light chain constant domain comprises or consists of the amino acid sequence of SEQ ID NO: 327 or SEQ ID NO:

328.

13. The antibody or antigen-binding fragment thereof of any previous claim, comprising the amino acid sequences of: a. SEQ ID NO: 333 and SEQ ID NO: 334; b. SEQ ID NO: 345 and SEQ ID NO: 346; c. SEQ ID NO: 351 and SEQ ID NO: 352; d. SEQ ID NO: 355 and SEQ ID NO:

356.

14. The antibody or antigen-binding fragment thereof of any previous claim, wherein the antibody is isolated and / or the antibody or antigen-binding fragment thereof is an scFv, Fab, Fab’, F(ab')2, Fv, variable domain (e.g. VH and / or VL), diabody, minibody or full length antibody.

15. The antibody or antigen-binding fragment thereof of any previous claim, wherein the antibody induces proliferation of gamma delta T cells, optionally a greater than 460-fold proliferation of gamma delta T cells (for example greater than 460-fold proliferation of gamma delta 3 TCR positive cells), and / or downregulation of gamma delta TCRs and / or promotes gamma delta T cell mediated killing (optionally THP-1 cell killing in co-culture assay).

16. The antibody or antigen-binding fragment thereof of any previous claim, wherein the antibody: a. specifically binds to delta 1 positive and delta 2 positive and delta 3 positive gamma delta TCRs; b. downregulates delta 1 positive and delta 2 positive and delta 3 positive gamma delta TCRs; and / or c. selectively activates and / or induces proliferation of delta 1 positive and delta 2 positive and delta 3 positive gamma delta cells.

17. The antibody or antigen-binding fragment thereof of any previous claim, wherein the antibody induces proliferation and / or TCR downregulation of gamma constant 2 positive cells but not gamma constant 1 positive cells.

18. A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof as defined in any one of claims 1 to 17 and a pharmaceutically acceptable diluent or carrier.

19. A kit comprising the antibody or antigen-binding fragment thereof of any one of claims 1 to 17, or the pharmaceutical composition of claim 18, optionally further comprising an additional therapeutically active agent.

20. The antibody or antigen-binding fragment thereof of any one of claims 1 to 17, or the pharmaceutical composition of claim 18 or the kit of claim 19 for use in a method of treating a disease or disorder in a subject, optionally wherein the disease is cancer.

21. A method of treating a disease or disorder in a subject, comprising administering to the subject the antibody or antigen-binding fragment thereof of any one of claims 1 to 17, or the pharmaceutical composition of claim 18, optionally wherein the disease or disorder is cancer.

22. A method of determining whether a patient is a suitable recipient of an anti-gamma delta antibody medicament, the method comprising: a. measuring the level of a constant domain biomarker (TRDC, TRGC1 or TRGC2) in a blood sample that has been obtained from a patient; b. determining the level of this biomarker is above a suitable threshold; c. recommending the patient for treatment with an antibody medicament which binds the constant domain of a gamma delta TCR positive immune cell.

23. A method of assessing a treatment regimen without a tissue biopsy is provided, the method comprising a. providing a blood sample that has been obtained from a patient to whom an antibody of the invention (an anti-TRDC, an anti-TRGC1 or an anti-TRGC2 antibody) has been administered; b. analysing the Vδ2+ gamma delta cells in the blood sample to confirm the administered antibody has engaged with the gamma delta cells; c. using this analysis to inform the treatment regimen for the patient.

24. The method of claim 22, wherein the level of biomarker is measured using an antibody of any one of claims 1 to 17.

25. The method of claim 22, wherein the antibody medicament is an anti-TRDC antibody, an anti- TRGC1 antibody or an anti-TRGC2 antibody, optionally wherein the antibody medicament is an antibody of any one of claims 1 to 17.

26. A nucleic acid that encodes an antibody or antigen binding fragment as defined in any of claims 1 to 17.

27. A vector comprising the nucleic acid as defined in claim 26, optionally wherein the vector is a CHO vector or HEK293 vector.

28. A host cell comprising the vector as defined in claim 27, optionally wherein the host cell is a CHO cell or HEK293 cell.

29. A method of producing an antibody or antigen binding fragment as defined in any of claims 1 to 17, comprising culturing the vector of claim 27 or the host cell of claim 28 under conditions allowing expression of the antibody or fragment and recovering the antibody or fragment.

30. An antibody or antigen-binding fragment of claims 1-20 comprising a hinge disabled Fc region, optionally comprising L235A, G237A mutations (according to Eu numbering).

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