Carrillo-Bustamante Paola, Keşmir Can, de Boer Rob J
Theoretical Biology & Bioinformatics, Department of Biology, Utrecht University, Utrecht, The Netherlands.
Center for Modeling and Simulation in the Biosciences, Bio-Quant Center, Heidelberg University, Heidelberg, Germany.
Immunogenetics. 2016 Jan;68(1):3-18. doi: 10.1007/s00251-015-0869-7. Epub 2015 Sep 21.
Natural killer (NK) cells are immune cells that play a crucial role against viral infections and tumors. To be tolerant against healthy tissue and simultaneously attack infected cells, the activity of NK cells is tightly regulated by a sophisticated array of germline-encoded activating and inhibiting receptors. The best characterized mechanism of NK cell activation is "missing self" detection, i.e., the recognition of virally infected or transformed cells that reduce their MHC expression to evade cytotoxic T cells. To monitor the expression of MHC-I on target cells, NK cells have monomorphic inhibitory receptors which interact with conserved MHC molecules. However, there are other NK cell receptors (NKRs) encoded by gene families showing a remarkable genetic diversity. Thus, NKR haplotypes contain several genes encoding for receptors with activating and inhibiting signaling, and that vary in gene content and allelic polymorphism. But if missing-self detection can be achieved by a monomorphic NKR system why have these polygenic and polymorphic receptors evolved? Here, we review the expansion of NKR receptor families in different mammal species, and we discuss several hypotheses that possibly underlie the diversification of the NK cell receptor complex, including the evolution of viral decoys, peptide sensitivity, and selective MHC-downregulation.
自然杀伤（NK）细胞是一种免疫细胞，在对抗病毒感染和肿瘤方面发挥着关键作用。为了耐受健康组织并同时攻击受感染细胞，NK细胞的活性受到一系列由种系编码的激活和抑制受体的严格调控。NK细胞激活的最典型机制是“自我缺失”检测，即识别那些降低其MHC表达以逃避细胞毒性T细胞的病毒感染或转化细胞。为了监测靶细胞上MHC-I的表达，NK细胞具有与保守MHC分子相互作用的单态抑制性受体。然而，还有其他由基因家族编码的NK细胞受体（NKR），显示出显著的遗传多样性。因此，NKR单倍型包含几个编码具有激活和抑制信号传导受体的基因，并且在基因含量和等位基因多态性方面存在差异。但是，如果单态NKR系统可以实现“自我缺失”检测，那么这些多基因和多态性受体为什么会进化呢？在这里，我们回顾了不同哺乳动物物种中NKR受体家族的扩展，并讨论了可能是NK细胞受体复合体多样化基础的几种假说，包括病毒诱饵的进化、肽敏感性和选择性MHC下调。
