2023-02-15 カロリンスカ研究所(KI)
◆私たちの免疫システムの一部であるT細胞は、感染症や癌から身を守るために中心的な役割を担っています。TCRの助けを借りて、細胞は外来の侵入者や腫瘍細胞を認識する。
◆研究者らは、血液サンプルのディープシーケンスを用いて、サハラ以南のアフリカ、東アジア、南アジア、ヨーロッパ出身の45人のTCR遺伝子を調査した。その結果、これらの遺伝子は、人や集団によって大きく異なることが明らかになった。この結果は、1000人ゲノムプロジェクトで得られた数千の追加症例の解析によっても確認された。
◆今回得られた知見と研究者らが公開した新しいTCR遺伝子データベースは、今後、新たな治療法の開発に大きく貢献する可能性がある。
<関連情報>
- https://news.ki.se/genetic-study-unexpectedly-high-variation-in-t-cell-receptor-genes-between-persons
- https://www.cell.com/immunity/fulltext/S1074-7613(23)00038-9
古代の人類は現代人のT細胞受容体遺伝子の大規模な変異に寄与してきた Archaic humans have contributed to large-scale variation in modern human T cell receptor genes
Martin Corcoran,,Mark Chernyshev,Marco Mandolesi ,Sanjana Narang,Mateusz Kaduk,Kewei Ye,Christopher Sundling,Anna Färnert,Taras Kreslavsky,Carolina Bernhardsson,Maximilian Larena,Mattias Jakobsson,Gunilla B. Karlsson Hedestam
Immunity Published:February 15, 2023
DOI:https://doi.org/10.1016/j.immuni.2023.01.026
Highlights
•Extensive human TCR gene heterogeneity exists in both populations and individuals
•TCR gene variations frequently involve coding changes and non-functional alleles
•Neanderthal-derived TCR regions are found in some modern human populations
•A frequent Neanderthal-derived TRGV4 variant mediates reduced BTNL3 ligand reactivity
Summary
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.
