人类T细胞受体（TCR）对调节自身抗原识别、介导对病原体和肿瘤的免疫反应至关重要。但是，编码TCR基因的变异仍未得到足够定义。详细分析了来自四个人类种群-非洲、东亚、南亚和欧洲的45个供体中表达的TCR α、β、γ和δ基因，发现了175个额外的TCR可变和连接桥段等位基因。其中大多数含有编码变化，并以不同的频率存在于人口中，这一发现得到了来自1000基因组计划的DNA样本的证实。重要的是，我们确定了三个新月旧石器时代的、内介基因的TCR区域，包括高度变异的TRGV4变体，它介导了改变的乳清蛋白样分子3 (BTNL3) 的配基反应，并在所有现代欧亚人群中普遍存在。我们的结果展示了TCR基因在个体和人口中的显著变异，为将等位基因变异纳入人类生物学中TCR功能研究提供了强有力的动力。版权所有©2023作者。Elsevier Inc.保留所有权利。

Human T cell receptors (TCRs) are critical for mediating immune responses to pathogens and tumors and regulating self-antigen recognition. Yet, variations in the genes encoding TCRs remain insufficiently defined. Detailed analysis of expressed TCR alpha, beta, gamma, and delta genes in 45 donors from four human populations-African, East Asian, South Asian, and European-revealed 175 additional TCR variable and junctional alleles. Most of these contained coding changes and were present at widely differing frequencies in the populations, a finding confirmed using DNA samples from the 1000 Genomes Project. Importantly, we identified three Neanderthal-derived, introgressed TCR regions including a highly divergent TRGV4 variant, which mediated altered butyrophilin-like molecule 3 (BTNL3) ligand reactivity and was frequent in all modern Eurasian population groups. Our results demonstrate remarkable variation in TCR genes in both individuals and populations, providing a strong incentive for including allelic variation in studies of TCR function in human biology.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.