Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma
2020
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
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.
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