TY - JOUR TI - Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma AU - Murata, Kenji AU - Nakatsugawa, Munehide AU - Rahman, Muhammed A AU - Nguyen, Linh T AU - Millar, Douglas G AU - Mulder, David T AU - Sugata, Kenji AU - Saijo, Hiroshi AU - Matsunaga, Yukiko AU - Kagoya, Yuki AU - Guo, Tingxi AU - Anczurowski, Mark AU - Wang, Chung-Hsi AU - Burt, Brian D AU - Ly, Dalam AU - Saso, Kayoko AU - Easson, Alexandra AU - Goldstein, David P AU - Reedijk, Michael AU - Ghazarian, Danny AU - Pugh, Trevor J AU - Butler, Marcus O AU - Mak, Tak W AU - Ohashi, Pamela S AU - Hirano, Naoto A2 - Kroemer, Guido A2 - Settleman, Jeffrey A2 - Sachidanandam, Ravi A2 - Odunsi, Kunle VL - 9 PY - 2020 DA - 2020/04/21 SP - e53244 C1 - eLife 2020;9:e53244 DO - 10.7554/eLife.53244 UR - https://doi.org/10.7554/eLife.53244 AB - HLA-restricted T cell responses can induce antitumor effects in cancer patients. Previous human T cell research has largely focused on the few HLA alleles prevalent in a subset of ethnic groups. Here, using a panel of newly developed peptide-exchangeable peptide/HLA multimers and artificial antigen-presenting cells for 25 different class I alleles and greater than 800 peptides, we systematically and comprehensively mapped shared antigenic epitopes recognized by tumor-infiltrating T lymphocytes (TILs) from eight melanoma patients for all their class I alleles. We were able to determine the specificity, on average, of 12.2% of the TILs recognizing a mean of 3.1 shared antigen-derived epitopes across HLA-A, B, and C. Furthermore, we isolated a number of cognate T cell receptor genes with tumor reactivity. Our novel strategy allows for a more complete examination of the immune response and development of novel cancer immunotherapy not limited by HLA allele prevalence or tumor mutation burden. KW - peptide/HLA multimer KW - artificial anitgen-presenting cell KW - melanoma KW - T cell receptor KW - shared antigenic epitope KW - tumor-infiltrating T lymphocyte JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -