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Genetic and environmental determinants of human TCR repertoire diversity.
Immunity & Ageing ( IF 7.9 ) Pub Date : 2020-09-04 , DOI: 10.1186/s12979-020-00195-9
Chirag Krishna 1, 2 , Diego Chowell 2, 3 , Mithat Gönen 4 , Yuval Elhanati 3, 4 , Timothy A Chan 2, 3, 5, 6, 7
Affiliation  

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.

中文翻译:

人类TCR谱表多样性的遗传和环境决定因素。

自我和非自我的T细胞区分是适应性免疫反应的基础,并且由主要组织相容性(MHC)分子呈现的T细胞受体(TCR)与它们的同源配体之间的相互作用来协调。然而,宿主免疫遗传变异对TCR库的多样性的影响尚不清楚。在这里,我们分析了TCR曲目库测序的666个人。我们显示TCR曲目库多样性与人类白血球抗原I类(HLA-1)基因座的多态性正相关,并随着年龄和巨细胞病毒(CMV)感染而减少。此外,我们的分析表明,HLA-1多态性和年龄独立影响健康个体的库。我们的数据阐明了人类TCR曲目库多样性的关键决定因素,
更新日期:2020-09-05
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