Rodriguez-Valbuena Henry, Salcedo Jorge, De Their Olivier, Flot Jean Francois, Tiozzo Stefano, De Tomaso Anthony W
Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA, USA.
Evolutionary Biology & Ecology, C.P. 160/12, Université libre de Bruxelles (ULB), Avenue F.D. Roosevelt 50, B-1050 Brussels, Belgium.
bioRxiv. 2024 Oct 18:2024.10.16.618699. doi: 10.1101/2024.10.16.618699.
Allorecognition in is controlled by a highly polymorphic locus (the ), and functionally similar to missing-self recognition utilized by Natural Killer cells-compatibility is determined by sharing a self-allele, and integration of activating and inhibitory signals determines outcome. We had found these signals were generated by two -encoded receptors, called and Here we show that genes are members of an extended family consisting of >37 loci, and co-expressed with an even more diverse gene family-the (). The are membrane proteins related to , but include conserved tyrosine motifs, including ITIMs and hemITAMs. Both genes are encoded in highly polymorphic haplotypes on multiple chromosomes, revealing an unparalleled level of diversity of innate receptors. Our results also suggest that ITAM/ITIM signal integration is a deeply conserved mechanism that has allowed convergent evolution of innate and adaptive cell-based recognition systems.
[具体生物名称]中的同种异体识别由一个高度多态的基因座（[具体基因座名称]）控制，其功能类似于自然杀伤细胞利用的缺失自我识别——相容性由共享一个自我等位基因决定，激活信号和抑制信号的整合决定结果。我们发现这些信号由两个[具体基因座名称]编码的受体产生，称为[受体名称1]和[受体名称2]。在此我们表明，[具体基因座名称]基因是一个由超过37个基因座组成的扩展家族的成员，并与一个更加多样化的基因家族——[具体基因家族名称]（[基因家族缩写]）共同表达。[具体基因家族名称]是与[相关蛋白名称]相关的膜蛋白，但包括保守的酪氨酸基序，包括免疫酪氨酸抑制基序（ITIMs）和半免疫酪氨酸激活基序（hemITAMs）。这两个基因都编码在多条染色体上的高度多态单倍型中，揭示了先天受体前所未有的多样性水平。我们的结果还表明，免疫酪氨酸激活基序/免疫酪氨酸抑制基序信号整合是一种深度保守的机制，它允许基于先天和适应性细胞的识别系统趋同进化。
