%0 Journal Article
%T Generation and molecular recognition of melanoma-associated antigen-specific human ¦Ã¦Ä T cells
%J -
%D 2018
%R 10.1126/sciimmunol.aav4036
%X Antigen recognition by T cells bearing ¦Á¦Â T cell receptors (TCRs) is restricted by major histocompatibility complex (MHC). However, how antigens are recognized by T cells bearing ¦Ã¦Ä TCRs remains unclear. Although ¦Ã¦Ä 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 ¦Ã¦Ä T cells in an MHC-restricted fashion. Cloning and transferring of MART-1¨Cspecific ¦Ã¦Ä 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¨Cspecific ¦Ã¦Ä TCR, together with MHC/peptide, revealed distinctive but similar docking properties to those previously reported for ¦Á¦Â TCRs, recognizing MART-1 on HLA-A*0201. Our work shows that antigen-specific and MHC-restricted ¦Ã¦Ä T cells can be generated in vitro and that MART-1¨Cspecific ¦Ã¦Ä T cells can also be found and cloned from the na£¿ve repertoire. These findings reveal that classical MHC-restricted human ¦Ã¦Ä TCRs exist in the periphery and have the potential to be used in developing of new TCR-based immunotherapeutic approaches
%U http://immunology.sciencemag.org/content/3/30/eaav4036