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

ABSTRACT: 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.

SUBMITTER: Murata K

PROVIDER: S-EPMC7234812 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

Murata Kenji K Nakatsugawa Munehide M Rahman Muhammed A MA Nguyen Linh T LT Millar Douglas G DG Mulder David T DT Sugata Kenji K Saijo Hiroshi H Matsunaga Yukiko Y Kagoya Yuki Y Guo Tingxi T Anczurowski Mark M Wang Chung-Hsi CH Burt Brian D BD Ly Dalam D Saso Kayoko K Easson Alexandra A Goldstein David P DP Reedijk Michael M Ghazarian Danny D Pugh Trevor J TJ Butler Marcus O MO Mak Tak W TW Ohashi Pamela S PS Hirano Naoto N

eLife 20200421

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 ( ...[more]

PMID: 32314731

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Dataset Information

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

Publications

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

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