Barclay A Neil, Hatherley Deborah
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Immunity. 2008 Nov 14;29(5):675-8. doi: 10.1016/j.immuni.2008.10.004.
Paired receptors are families of membrane proteins containing similar extracellular regions but differing in their potential for signaling with one type able to give inhibitory signals and the other activating. Inhibitory receptors could be good targets for pathogens to restrict immune responses against them. Here we suggest that activating members may have evolved to counterbalance pathogens utilizing the inhibitory pathway. Thus, if a pathogen utilizes any part of the inhibitory receptor to downregulate responses against itself, it may, because of similarities in structure, also bind the activating receptor and give an opposing signal. We evaluate recent structural data on SIRPalpha (signal regulatory protein) and LILRB1 (leukocyte immunoglobulin-like receptor subfamily B member 1) showing evidence of pathogen pressure in nonligand-binding regions of these receptors together with data on pathogen binding to PIRs (paired Ig-like receptors) to provide support for this theory.
配对受体是一类膜蛋白家族，其胞外区域相似，但信号传导潜力不同，其中一种能够发出抑制性信号，另一种则能发出激活信号。抑制性受体可能是病原体限制针对它们的免疫反应的良好靶点。在此我们提出，激活型成员可能已经进化以平衡利用抑制性途径的病原体。因此，如果病原体利用抑制性受体的任何部分来下调针对自身的反应，由于结构相似，它可能也会结合激活型受体并发出相反的信号。我们评估了关于信号调节蛋白α（SIRPα）和白细胞免疫球蛋白样受体亚家族B成员1（LILRB1）的最新结构数据，这些数据显示了这些受体非配体结合区域存在病原体压力的证据，同时还有病原体与配对免疫球蛋白样受体（PIR）结合的数据，以此为该理论提供支持。
