Genetic and environmental determinants of human TCR repertoire diversity.
Aging
Heterozygote advantage
Immunogenetics
Infection
Major histocompatibility complex
T cell receptor repertoire
Journal
Immunity & ageing : I & A
ISSN: 1742-4933
Titre abrégé: Immun Ageing
Pays: England
ID NLM: 101235427
Informations de publication
Date de publication:
2020
2020
Historique:
received:
14
05
2020
accepted:
06
08
2020
entrez:
18
9
2020
pubmed:
19
9
2020
medline:
19
9
2020
Statut:
epublish
Résumé
T cell discrimination of self and non-self is the foundation of the adaptive immune response, and is orchestrated by the interaction between T cell receptors (TCRs) and their cognate ligands presented by major histocompatibility (MHC) molecules. However, the impact of host immunogenetic variation on the diversity of the TCR repertoire remains unclear. Here, we analyzed a cohort of 666 individuals with TCR repertoire sequencing. We show that TCR repertoire diversity is positively associated with polymorphism at the human leukocyte antigen class I (HLA-I) loci, and diminishes with age and cytomegalovirus (CMV) infection. Moreover, our analysis revealed that HLA-I polymorphism and age independently shape the repertoire in healthy individuals. Our data elucidate key determinants of human TCR repertoire diversity, and suggest a mechanism underlying the evolutionary fitness advantage of HLA-I heterozygosity.
Identifiants
pubmed: 32944053
doi: 10.1186/s12979-020-00195-9
pii: 195
pmc: PMC7487954
doi:
Types de publication
Journal Article
Langues
eng
Pagination
26Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© The Author(s) 2020.
Déclaration de conflit d'intérêts
Competing interestsNot applicable.
Références
Proc Natl Acad Sci U S A. 2019 Oct 29;116(44):22252-22261
pubmed: 31570608
BMC Biotechnol. 2017 Jul 10;17(1):61
pubmed: 28693542
Nucleic Acids Res. 2015 Jan;43(Database issue):D423-31
pubmed: 25414341
Front Immunol. 2019 Aug 30;10:2064
pubmed: 31543879
Genome Med. 2013 Oct 30;5(10):98
pubmed: 24172704
Nat Med. 2019 Nov;25(11):1715-1720
pubmed: 31700181
Proc Natl Acad Sci U S A. 2020 Jan 7;117(1):532-540
pubmed: 31879353
Nature. 1988 Nov 17;336(6196):222-5
pubmed: 3143074
Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13139-44
pubmed: 25157137
Science. 2019 Nov 1;366(6465):599-606
pubmed: 31672891
Front Immunol. 2019 Jul 31;10:1516
pubmed: 31417541
Annu Rev Immunol. 2006;24:419-66
pubmed: 16551255
J Immunol. 2014 Mar 15;192(6):2689-98
pubmed: 24510963
Nature. 1988 Aug 4;334(6181):395-402
pubmed: 3043226
Nat Immunol. 2007 Sep;8(9):975-83
pubmed: 17694060
PLoS Biol. 2003 Oct;1(1):E16
pubmed: 14551913
Proc Natl Acad Sci U S A. 2018 Feb 27;115(9):2168-2173
pubmed: 29440397
Blood. 2009 Nov 5;114(19):4099-107
pubmed: 19706884
Sci Transl Med. 2012 Apr 4;4(128):128ra42
pubmed: 22491952
Curr Genomics. 2007 Nov;8(7):453-65
pubmed: 19412418
Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10896-9
pubmed: 1438295
Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):E10702-E10711
pubmed: 30348802
Elife. 2018 Aug 28;7:
pubmed: 30152754
Proc Natl Acad Sci U S A. 2014 Jul 8;111(27):9875-80
pubmed: 24941953
Cell. 1987 Apr 24;49(2):273-80
pubmed: 3494522
Nat Rev Immunol. 2008 Mar;8(3):231-8
pubmed: 18301425
Philos Trans R Soc Lond B Biol Sci. 2009 Jan 12;364(1513):117-28
pubmed: 18926972
Nature. 1999 Nov 18;402(6759):255-62
pubmed: 10580495
Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11260-4
pubmed: 12177415
Science. 1999 Mar 12;283(5408):1748-52
pubmed: 10073943
Nature. 2009 Apr 23;458(7241):1043-6
pubmed: 19262510
PLoS Comput Biol. 2015 Nov 25;11(11):e1004503
pubmed: 26606115
Lancet Infect Dis. 2004 Dec;4(12):725-38
pubmed: 15567122
J Immunol. 2005 Jun 1;174(11):7446-52
pubmed: 15905594
Mol Biol Evol. 2018 Sep 1;35(9):2145-2158
pubmed: 29893875
Immunol Rev. 2018 Jul;284(1):167-179
pubmed: 29944757
Nat Genet. 2016 Sep;48(9):995-1002
pubmed: 27479906
Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16671-6
pubmed: 18946038
Science. 1974 Sep 6;185(4154):862-4
pubmed: 4843792
Nucleic Acids Res. 2018 Jan 4;46(D1):D754-D761
pubmed: 29155950
Nat Genet. 2017 May;49(5):659-665
pubmed: 28369038
Lancet. 1975 Jun 28;1(7922):1406-9
pubmed: 49564
Proc Natl Acad Sci U S A. 2019 Mar 12;116(11):5021-5026
pubmed: 30796191
Cell. 2005 Jul 29;122(2):247-60
pubmed: 16051149
Science. 1999 Oct 29;286(5441):958-61
pubmed: 10542151
Genome Res. 2011 May;21(5):790-7
pubmed: 21349924
Eur J Immunol. 2003 Dec;33(12):3353-8
pubmed: 14635043
Science. 2018 Feb 2;359(6375):582-587
pubmed: 29217585
Nucleic Acids Res. 2004 Mar 19;32(5):1792-7
pubmed: 15034147
Sci Transl Med. 2010 Sep 1;2(47):47ra64
pubmed: 20811043
Eur J Immunol. 1971 Jan;1(1):1-9
pubmed: 14978855