Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals

Abstract To expand our knowledge of the ontogeny of the T-cell receptor (TCR) repertoire of antigen-specific T-cell subsets, we combined next-generation deep sequencing and single-cell multiplex clonotype analysis to evaluate the diversity and frequency of paired TCRs, their functions and whether cl...

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Autores principales:	Takahiko Miyama, Takakazu Kawase, Kazutaka Kitaura, Ren Chishaki, Masashi Shibata, Kumi Oshima, Hiroshi Hamana, Hiroyuki Kishi, Atsushi Muraguchi, Kiyotaka Kuzushima, Hiroh Saji, Tadasu Shin-I, Ryuji Suzuki, Tatsuo Ichinohe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0969cf375aa9446493eb78cd67bba44f
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spelling	oai:doaj.org-article:0969cf375aa9446493eb78cd67bba44f2021-12-02T12:32:45ZHighly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals10.1038/s41598-017-03855-x2045-2322https://doaj.org/article/0969cf375aa9446493eb78cd67bba44f2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03855-xhttps://doaj.org/toc/2045-2322Abstract To expand our knowledge of the ontogeny of the T-cell receptor (TCR) repertoire of antigen-specific T-cell subsets, we combined next-generation deep sequencing and single-cell multiplex clonotype analysis to evaluate the diversity and frequency of paired TCRs, their functions and whether clonotypic TCRs are shared among different individuals. Using an HLA-A02-restricted cytomegalovirus (CMV) pp65-derived immunogenic peptide, we found that the more dominant pp65-specific TCR clonotypes in the blood of healthy donors have higher binding affinities for the CMV peptide and arise from clonotypes that are highly shared among individuals. Interestingly, these highly shared HLA-A02-restricted CMV-specific TCRs were detected in a CMV-seronegative individual as well as in HLA-A*02-negative donors albeit at lower frequency. More intriguingly, these shared TCR clonotypes were abundant in the stem memory T-cell subset, and TCR diversity of the stem memory T-cell repertoire was significantly lower than in the central memory and effector memory T-cell repertoires. These results suggest that the stem memory T-cell subset may serve as a reservoir of highly shared and highly functional memory T-cells.Takahiko MiyamaTakakazu KawaseKazutaka KitauraRen ChishakiMasashi ShibataKumi OshimaHiroshi HamanaHiroyuki KishiAtsushi MuraguchiKiyotaka KuzushimaHiroh SajiTadasu Shin-IRyuji SuzukiTatsuo IchinoheNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takahiko Miyama Takakazu Kawase Kazutaka Kitaura Ren Chishaki Masashi Shibata Kumi Oshima Hiroshi Hamana Hiroyuki Kishi Atsushi Muraguchi Kiyotaka Kuzushima Hiroh Saji Tadasu Shin-I Ryuji Suzuki Tatsuo Ichinohe Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals
description	Abstract To expand our knowledge of the ontogeny of the T-cell receptor (TCR) repertoire of antigen-specific T-cell subsets, we combined next-generation deep sequencing and single-cell multiplex clonotype analysis to evaluate the diversity and frequency of paired TCRs, their functions and whether clonotypic TCRs are shared among different individuals. Using an HLA-A02-restricted cytomegalovirus (CMV) pp65-derived immunogenic peptide, we found that the more dominant pp65-specific TCR clonotypes in the blood of healthy donors have higher binding affinities for the CMV peptide and arise from clonotypes that are highly shared among individuals. Interestingly, these highly shared HLA-A02-restricted CMV-specific TCRs were detected in a CMV-seronegative individual as well as in HLA-A*02-negative donors albeit at lower frequency. More intriguingly, these shared TCR clonotypes were abundant in the stem memory T-cell subset, and TCR diversity of the stem memory T-cell repertoire was significantly lower than in the central memory and effector memory T-cell repertoires. These results suggest that the stem memory T-cell subset may serve as a reservoir of highly shared and highly functional memory T-cells.
format	article
author	Takahiko Miyama Takakazu Kawase Kazutaka Kitaura Ren Chishaki Masashi Shibata Kumi Oshima Hiroshi Hamana Hiroyuki Kishi Atsushi Muraguchi Kiyotaka Kuzushima Hiroh Saji Tadasu Shin-I Ryuji Suzuki Tatsuo Ichinohe
author_facet	Takahiko Miyama Takakazu Kawase Kazutaka Kitaura Ren Chishaki Masashi Shibata Kumi Oshima Hiroshi Hamana Hiroyuki Kishi Atsushi Muraguchi Kiyotaka Kuzushima Hiroh Saji Tadasu Shin-I Ryuji Suzuki Tatsuo Ichinohe
author_sort	Takahiko Miyama
title	Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals
title_short	Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals
title_full	Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals
title_fullStr	Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals
title_full_unstemmed	Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals
title_sort	highly functional t-cell receptor repertoires are abundant in stem memory t cells and highly shared among individuals
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0969cf375aa9446493eb78cd67bba44f
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Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals

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