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

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-...

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Autores principales: Murata, Kenji, Nakatsugawa, Munehide, Rahman, Muhammed A, Nguyen, Linh T, Millar, Douglas G, Mulder, David T, Sugata, Kenji, Saijo, Hiroshi, Matsunaga, Yukiko, Kagoya, Yuki, Guo, Tingxi, Anczurowski, Mark, Wang, Chung-Hsi, Burt, Brian D, Ly, Dalam, Saso, Kayoko, Easson, Alexandra, Goldstein, David P, Reedijk, Michael, Ghazarian, Danny, Pugh, Trevor J, Butler, Marcus O, Mak, Tak W, Ohashi, Pamela S, Hirano, Naoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234812/
https://www.ncbi.nlm.nih.gov/pubmed/32314731
http://dx.doi.org/10.7554/eLife.53244
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author Murata, Kenji
Nakatsugawa, Munehide
Rahman, Muhammed A
Nguyen, Linh T
Millar, Douglas G
Mulder, David T
Sugata, Kenji
Saijo, Hiroshi
Matsunaga, Yukiko
Kagoya, Yuki
Guo, Tingxi
Anczurowski, Mark
Wang, Chung-Hsi
Burt, Brian D
Ly, Dalam
Saso, Kayoko
Easson, Alexandra
Goldstein, David P
Reedijk, Michael
Ghazarian, Danny
Pugh, Trevor J
Butler, Marcus O
Mak, Tak W
Ohashi, Pamela S
Hirano, Naoto
author_facet Murata, Kenji
Nakatsugawa, Munehide
Rahman, Muhammed A
Nguyen, Linh T
Millar, Douglas G
Mulder, David T
Sugata, Kenji
Saijo, Hiroshi
Matsunaga, Yukiko
Kagoya, Yuki
Guo, Tingxi
Anczurowski, Mark
Wang, Chung-Hsi
Burt, Brian D
Ly, Dalam
Saso, Kayoko
Easson, Alexandra
Goldstein, David P
Reedijk, Michael
Ghazarian, Danny
Pugh, Trevor J
Butler, Marcus O
Mak, Tak W
Ohashi, Pamela S
Hirano, Naoto
author_sort Murata, Kenji
collection PubMed
description 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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spelling pubmed-72348122020-05-20 Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma Murata, Kenji Nakatsugawa, Munehide Rahman, Muhammed A Nguyen, Linh T Millar, Douglas G Mulder, David T Sugata, Kenji Saijo, Hiroshi Matsunaga, Yukiko Kagoya, Yuki Guo, Tingxi Anczurowski, Mark Wang, Chung-Hsi Burt, Brian D Ly, Dalam Saso, Kayoko Easson, Alexandra Goldstein, David P Reedijk, Michael Ghazarian, Danny Pugh, Trevor J Butler, Marcus O Mak, Tak W Ohashi, Pamela S Hirano, Naoto eLife Immunology and Inflammation 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. eLife Sciences Publications, Ltd 2020-04-21 /pmc/articles/PMC7234812/ /pubmed/32314731 http://dx.doi.org/10.7554/eLife.53244 Text en © 2020, Murata et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology and Inflammation
Murata, Kenji
Nakatsugawa, Munehide
Rahman, Muhammed A
Nguyen, Linh T
Millar, Douglas G
Mulder, David T
Sugata, Kenji
Saijo, Hiroshi
Matsunaga, Yukiko
Kagoya, Yuki
Guo, Tingxi
Anczurowski, Mark
Wang, Chung-Hsi
Burt, Brian D
Ly, Dalam
Saso, Kayoko
Easson, Alexandra
Goldstein, David P
Reedijk, Michael
Ghazarian, Danny
Pugh, Trevor J
Butler, Marcus O
Mak, Tak W
Ohashi, Pamela S
Hirano, Naoto
Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma
title Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma
title_full Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma
title_fullStr Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma
title_full_unstemmed Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma
title_short Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma
title_sort landscape mapping of shared antigenic epitopes and their cognate tcrs of tumor-infiltrating t lymphocytes in melanoma
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234812/
https://www.ncbi.nlm.nih.gov/pubmed/32314731
http://dx.doi.org/10.7554/eLife.53244
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