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'Remarkable' Variation Found in Human T Cell Receptor Genes

An investigation into the genetics of human T cell receptors (TCRs) in Immunity this week uncovered intriguing variation. Understanding variation within the immune system is key to the study of disease susceptibility, prognosis, and population history. However, research into genetic diversity within the immune system has largely been limited to genes that encode innate immune functions and the major histocompatibility complex genes. To expand knowledge around gene variation in TCRs, Karolinska Institute scientists used repertoire sequencing and other approaches to analyze expressed TCR genes in 45 people of African, East Asian, South Asian, and European descent. They uncover higher diversity in expressed TCR variable, diversity, and joining genes than previously reported, with almost double the number of expressed TCR variable alleles than previously identified. Notably, the researchers also discovered three Neanderthal-derived, introgressed TCR regions in some of the modern humans. "The results of this study indicate that genetic diversity in the expressed TCR locus is extensive in both individuals and populations," the authors write. Expanding the catalog of human TCR genetic variation will "enable in-depth understanding of the functional role of this variation, helping to define critical components of TCR biology that may have been hitherto overlooked."

The Scan

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