6d7g
Structure of 5F3 TCR in complex with HLA-A2/MART-1
Structural highlights
Publication Abstract from PubMedAntigen recognition by T cells bearing alphabeta T cell receptors (TCRs) is restricted by major histocompatibility complex (MHC). However, how antigens are recognized by T cells bearing gammadelta TCRs remains unclear. Although gammadelta T cells can recognize nonclassical MHC, it is generally thought that recognition of antigens is not MHC restricted. Here, we took advantage of an in vitro system to generate antigen-specific human T cells and show that melanoma-associated antigens, MART-1 and gp100, can be recognized by gammadelta T cells in an MHC-restricted fashion. Cloning and transferring of MART-1-specific gammadelta TCRs restored the specific recognition of the initial antigen MHC/peptide reactivity and conferred antigen-specific functional responses. A crystal structure of a MART-1-specific gammadelta TCR, together with MHC/peptide, revealed distinctive but similar docking properties to those previously reported for alphabeta TCRs, recognizing MART-1 on HLA-A*0201. Our work shows that antigen-specific and MHC-restricted gammadelta T cells can be generated in vitro and that MART-1-specific gammadelta T cells can also be found and cloned from the naive repertoire. These findings reveal that classical MHC-restricted human gammadelta TCRs exist in the periphery and have the potential to be used in developing of new TCR-based immunotherapeutic approaches. Generation and molecular recognition of melanoma-associated antigen-specific human gammadelta T cells.,Benveniste PM, Roy S, Nakatsugawa M, Chen ELY, Nguyen L, Millar DG, Ohashi PS, Hirano N, Adams EJ, Zuniga-Pflucker JC Sci Immunol. 2018 Dec 14;3(30). pii: 3/30/eaav4036. doi:, 10.1126/sciimmunol.aav4036. PMID:30552102[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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