Impact of HLA type, age and chronic viral infection on peripheral T-cell receptor sharing between unrelated individuals.

The human adaptive immune system must generate extraordinary diversity to be able to respond to all possible pathogens. The T-cell repertoire derives this high diversity through somatic recombination of the T-cell receptor (TCR) locus, a random process that results in repertoires that are largely pr...

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Autores principales:	Sarah A Johnson, Spencer L Seale, Rachel M Gittelman, Julie A Rytlewski, Harlan S Robins, Paul A Fields
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dee177985d1643a8a813d6a4f72cdbb8
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spelling	oai:doaj.org-article:dee177985d1643a8a813d6a4f72cdbb82021-12-02T20:14:53ZImpact of HLA type, age and chronic viral infection on peripheral T-cell receptor sharing between unrelated individuals.1932-620310.1371/journal.pone.0249484https://doaj.org/article/dee177985d1643a8a813d6a4f72cdbb82021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0249484https://doaj.org/toc/1932-6203The human adaptive immune system must generate extraordinary diversity to be able to respond to all possible pathogens. The T-cell repertoire derives this high diversity through somatic recombination of the T-cell receptor (TCR) locus, a random process that results in repertoires that are largely private to each individual. However, factors such as thymic selection and T-cell proliferation upon antigen exposure can affect TCR sharing among individuals. By immunosequencing the TCRβ variable region of 426 healthy individuals, we find that, on average, fewer than 1% of TCRβ clones are shared between individuals, consistent with largely private TCRβ repertoires. However, we detect a significant correlation between increased HLA allele sharing and increased number of shared TCRβ clones, with each additional shared HLA allele contributing to an increase in ~0.01% of the total shared TCRβ clones, supporting a key role for HLA type in shaping the immune repertoire. Surprisingly, we find that shared antigen exposure to CMV leads to fewer shared TCRβ clones, even after controlling for HLA, indicative of a largely private response to major viral antigenic exposure. Consistent with this hypothesis, we find that increased age is correlated with decreased overall TCRβ clone sharing, indicating that the pattern of private TCRβ clonal expansion is a general feature of the T-cell response to other infectious antigens as well. However, increased age also correlates with increased sharing among the lowest frequency clones, consistent with decreased repertoire diversity in older individuals. Together, all of these factors contribute to shaping the TCRβ repertoire, and understanding their interplay has important implications for the use of T cells for therapeutics and diagnostics.Sarah A JohnsonSpencer L SealeRachel M GittelmanJulie A RytlewskiHarlan S RobinsPaul A FieldsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0249484 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah A Johnson Spencer L Seale Rachel M Gittelman Julie A Rytlewski Harlan S Robins Paul A Fields Impact of HLA type, age and chronic viral infection on peripheral T-cell receptor sharing between unrelated individuals.
description	The human adaptive immune system must generate extraordinary diversity to be able to respond to all possible pathogens. The T-cell repertoire derives this high diversity through somatic recombination of the T-cell receptor (TCR) locus, a random process that results in repertoires that are largely private to each individual. However, factors such as thymic selection and T-cell proliferation upon antigen exposure can affect TCR sharing among individuals. By immunosequencing the TCRβ variable region of 426 healthy individuals, we find that, on average, fewer than 1% of TCRβ clones are shared between individuals, consistent with largely private TCRβ repertoires. However, we detect a significant correlation between increased HLA allele sharing and increased number of shared TCRβ clones, with each additional shared HLA allele contributing to an increase in ~0.01% of the total shared TCRβ clones, supporting a key role for HLA type in shaping the immune repertoire. Surprisingly, we find that shared antigen exposure to CMV leads to fewer shared TCRβ clones, even after controlling for HLA, indicative of a largely private response to major viral antigenic exposure. Consistent with this hypothesis, we find that increased age is correlated with decreased overall TCRβ clone sharing, indicating that the pattern of private TCRβ clonal expansion is a general feature of the T-cell response to other infectious antigens as well. However, increased age also correlates with increased sharing among the lowest frequency clones, consistent with decreased repertoire diversity in older individuals. Together, all of these factors contribute to shaping the TCRβ repertoire, and understanding their interplay has important implications for the use of T cells for therapeutics and diagnostics.
format	article
author	Sarah A Johnson Spencer L Seale Rachel M Gittelman Julie A Rytlewski Harlan S Robins Paul A Fields
author_facet	Sarah A Johnson Spencer L Seale Rachel M Gittelman Julie A Rytlewski Harlan S Robins Paul A Fields
author_sort	Sarah A Johnson
title	Impact of HLA type, age and chronic viral infection on peripheral T-cell receptor sharing between unrelated individuals.
title_short	Impact of HLA type, age and chronic viral infection on peripheral T-cell receptor sharing between unrelated individuals.
title_full	Impact of HLA type, age and chronic viral infection on peripheral T-cell receptor sharing between unrelated individuals.
title_fullStr	Impact of HLA type, age and chronic viral infection on peripheral T-cell receptor sharing between unrelated individuals.
title_full_unstemmed	Impact of HLA type, age and chronic viral infection on peripheral T-cell receptor sharing between unrelated individuals.
title_sort	impact of hla type, age and chronic viral infection on peripheral t-cell receptor sharing between unrelated individuals.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/dee177985d1643a8a813d6a4f72cdbb8
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Impact of HLA type, age and chronic viral infection on peripheral T-cell receptor sharing between unrelated individuals.

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