Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Johnson, Sarah A., Seale, Spencer L., Gittelman, Rachel M., Rytlewski, Julie A., Robins, Harlan S., Fields, Paul A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405014/
https://www.ncbi.nlm.nih.gov/pubmed/34460826
http://dx.doi.org/10.1371/journal.pone.0249484
_version_ 1783746251194368000
author Johnson, Sarah A.
Seale, Spencer L.
Gittelman, Rachel M.
Rytlewski, Julie A.
Robins, Harlan S.
Fields, Paul A.
author_facet Johnson, Sarah A.
Seale, Spencer L.
Gittelman, Rachel M.
Rytlewski, Julie A.
Robins, Harlan S.
Fields, Paul A.
author_sort Johnson, Sarah A.
collection PubMed
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 Online
Article
Text
id pubmed-8405014
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-84050142021-08-31 Impact of HLA type, age and chronic viral infection on peripheral T-cell receptor sharing between unrelated individuals Johnson, Sarah A. Seale, Spencer L. Gittelman, Rachel M. Rytlewski, Julie A. Robins, Harlan S. Fields, Paul A. PLoS One Research Article 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. Public Library of Science 2021-08-30 /pmc/articles/PMC8405014/ /pubmed/34460826 http://dx.doi.org/10.1371/journal.pone.0249484 Text en © 2021 Johnson et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Johnson, Sarah A.
Seale, Spencer L.
Gittelman, Rachel M.
Rytlewski, Julie A.
Robins, Harlan S.
Fields, Paul A.
Impact of HLA type, age and chronic viral infection on peripheral T-cell receptor sharing between unrelated individuals
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405014/
https://www.ncbi.nlm.nih.gov/pubmed/34460826
http://dx.doi.org/10.1371/journal.pone.0249484
work_keys_str_mv AT johnsonsaraha impactofhlatypeageandchronicviralinfectiononperipheraltcellreceptorsharingbetweenunrelatedindividuals
AT sealespencerl impactofhlatypeageandchronicviralinfectiononperipheraltcellreceptorsharingbetweenunrelatedindividuals
AT gittelmanrachelm impactofhlatypeageandchronicviralinfectiononperipheraltcellreceptorsharingbetweenunrelatedindividuals
AT rytlewskijuliea impactofhlatypeageandchronicviralinfectiononperipheraltcellreceptorsharingbetweenunrelatedindividuals
AT robinsharlans impactofhlatypeageandchronicviralinfectiononperipheraltcellreceptorsharingbetweenunrelatedindividuals
AT fieldspaula impactofhlatypeageandchronicviralinfectiononperipheraltcellreceptorsharingbetweenunrelatedindividuals