Archaic humans have contributed to large-scale variation in modern human T cell receptor genes.

Bibliographic Collection: 
Publication Type: Journal Article
Authors: Corcoran, Martin; Chernyshev, Mark; Mandolesi, Marco; Narang, Sanjana; Kaduk, Mateusz; Ye, Kewei; Sundling, Christopher; Färnert, Anna; Kreslavsky, Taras; Bernhardsson, Carolina; Larena, Maximilian; Jakobsson, Mattias; Karlsson Hedestam, Gunilla B
Year of Publication: 2023
Journal: Immunity
Date Published: 2023 Feb 08
Publication Language: eng
ISSN: 1097-4180

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.

DOI: 10.1016/j.immuni.2023.01.026
Alternate Journal: Immunity