Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles
Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles
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DOI：
10.1016/j.jaut.2022.102907
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发表时间：
2022-09-18
影响因子：
12.8
通讯作者：
Fujio, Keishi
中科院分区：
文献类型：
--
作者：
Nagafuchi, Yasuo;Ota, Mineto;Fujio, Keishi
目的：人类白细胞抗原（HLA）等位基因调节类风湿关节炎（RA）和免疫介导疾病的易感性。本研究旨在阐明HLA等位基因对T细胞亚群的影响。方法：我们对ImmuNexUT数据库中13个纯化的T细胞亚群进行了全基因组和HLA等位基因相关性分析，包括407名患有10种免疫介导疾病的供体和健康对照。结果：HLA II类等位基因与TRBV基因使用和CD4 T细胞的公共克隆相关，而HLA I类等位基因与CD8 T细胞相关。RA风险和免疫介导的疾病风险HLA等位基因与初始和效应CD4 T细胞亚群的TRBV基因使用以及Th17中积累的公共克隆相关。克隆多样性是独立的HLA等位基因和转录组的变化，反映TCR signaling.Conclusion：这项研究揭示了在体内的证据表明，HLA等位基因和环境因素的形状天真和效应TCR剧目在RA和免疫介导的疾病患者。
Objective: Human Leukocyte Antigen (HLA) alleles regulate susceptibility to rheumatoid arthritis (RA) and immune-mediated diseases. This study aims to elucidate the impact of HLA alleles to T cell subsets.Methods: We performed genome-wide and HLA allele association analysis for T cell receptor (TCR) beta chain repertoire in 13 purified T cell subsets from the ImmuNexUT database, consisting of 407 donors with ten immune-mediated diseases and healthy controls.Results: HLA class II alleles were associated with TRBV gene usage and the public clones of CD4 T cells, while HLA class I alleles were associated with CD8 T cells. RA-risk and immune-mediated diseases-risk HLA alleles were associated with TRBV gene usage of naive and effector CD4 T cell subsets and public clones accumulating in Th17. Clonal diversity was independent of HLA alleles and was correlated with transcriptome changes that reflect TCR signaling.Conclusion: This study revealed in vivo evidence that both HLA alleles and environmental factors shape naive and effector TCR repertoires in RA and immune-mediated diseases patients.