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Open Access 01-12-2020 | Short report

Genetic and environmental determinants of human TCR repertoire diversity

Authors: Chirag Krishna, Diego Chowell, Mithat Gönen, Yuval Elhanati, Timothy A. Chan

Published in: Immunity & Ageing | Issue 1/2020

Abstract

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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Title: Genetic and environmental determinants of human TCR repertoire diversity
Authors: Chirag Krishna
Diego Chowell
Mithat Gönen
Yuval Elhanati
Timothy A. Chan
Publication date: 01-12-2020
Publisher: BioMed Central
Published in: Immunity & Ageing / Issue 1/2020
Electronic ISSN: 1742-4933
DOI: https://doi.org/10.1186/s12979-020-00195-9

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