Genetic and environmental determinants of human TCR repertoire diversity

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...

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Veröffentlicht in:Immunity & ageing Jg. 17; H. 1; S. 26 - 7
Hauptverfasser: Krishna, Chirag, Chowell, Diego, Gönen, Mithat, Elhanati, Yuval, Chan, Timothy A.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London BioMed Central 04.09.2020
BioMed Central Ltd
Springer Nature B.V
BMC
Schlagworte:
Adaptive immunity
Age
Aging
Analysis
Antibodies
Biomedical and Life Sciences
Biomedicine
Clinical Nutrition
Cytomegalovirus
Entropy
Genetic aspects
Geriatrics/Gerontology
Health aspects
Heterozygosity
Heterozygote advantage
Histocompatibility antigen HLA
HLA antigens
Hypotheses
Immune response
Immunogenetics
Immunology
Infection
Infections
Lymphocytes
Lymphocytes T
Major histocompatibility complex
Peptides
Polymorphism
Public Health
Short Report
T cell receptor repertoire
T cell receptors
T cells
Infection
Aging
T cell receptor repertoire
Immunogenetics
Major histocompatibility complex
Heterozygote advantage
ISSN:1742-4933, 1742-4933
Online-Zugang:Volltext
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Zusammenfassung: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.
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ISSN:1742-4933
1742-4933
DOI:10.1186/s12979-020-00195-9