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Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma

2020; eLife Sciences Publications Ltd; Volume: 9; Linguagem: Inglês

10.7554/elife.53244

2050-084X

Kenji Murata, Munehide Nakatsugawa, Muhammed A. Rahman, Linh T. Nguyen, Douglas G. Millar, David T. Mulder, Kenji Sugata, Hiroshi Saijo, Yukiko Matsunaga, Yuki Kagoya, Tingxi Guo, Mark Anczurowski, Chung-Hsi Wang, Brian D. Burt, Dalam Ly, Kayoko Saso, Alexandra Easson, David P. Goldstein, Michael Reedijk, Danny Ghazarian, Trevor J. Pugh, Marcus O. Butler, Tak W. Mak, Pamela S. Ohashi, Naoto Hirano,

vaccines and immunoinformatics approaches

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.