Ancient DNA shaped modern immune systems, study finds
Researchers discovered that genes inherited from archaic humans—Neanderthals and Denisovans—significantly influence T cell receptors in modern populations, affecting immune function across the globe. The finding could reshape how scientists understand disease susceptibility and vaccine response differences between populations.
Originaltitel: Archaic humans have contributed to large-scale variation in modern human T cell receptor genes
<p>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 <em>TRGV4</em> variant, which mediated altered butyrophilin-like molecule 3 (<em>BTNL3</em>) 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.</p>