期刊
IMMUNITY & AGEING
卷 17, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12979-020-00195-9
关键词
Major histocompatibility complex; Heterozygote advantage; T cell receptor repertoire; Infection; Aging; Immunogenetics
资金
- National Institutes of Health (NIH) [R35 CA232097]
- NIH [RO1 CA205426]
- PaineWebber Chair
- NIH/National Cancer Institute's Cancer Center support grant [P30 CA008748]
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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