Falco M, Moretta L, Moretta A, Bottino C
Istituto Giannina Gaslini, Genoa, Italy.
Tissue Antigens. 2013 Dec;82(6):363-73. doi: 10.1111/tan.12262.
Killer immunoglobulin-like receptors (KIRs) play an essential role in the regulation of natural killer (NK) activity, allowing NK cells to sense and respond to human leukocyte antigen (HLA) class I downregulation, an important hallmark for viral infections and tumor transformation. KIR and HLA genes are located on different chromosomes and KIR/HLA class I interaction represents an example of genetic epistasis in which the presence of receptor/ligand pairs is necessary for the induction of functional activity, while the presence of one in the absence of the other is not sufficient to influence NK cell function. Due to the high degree of HLA class I and KIR gene variability, KIR/KIR-ligand (KIR-L) interactions are extraordinarily diverse. KIR polymorphism arises from both haplotypic and allelic variations and was shaped by natural selection. KIR variability affects NK cell education influencing the KIR repertoire, KIR expression, the strength of KIR/KIR-L interactions and the capability to deliver signals. Moreover, it may influence NK cell function during infections, autoimmune diseases, pregnancy and allogeneic transplantation. This review summarizes the genetic and functional features of KIR/KIR-L interactions and gives an overview of their potential relevance in clinical studies.
杀伤细胞免疫球蛋白样受体（KIR）在自然杀伤（NK）活性的调节中起着至关重要的作用，使NK细胞能够感知并响应人类白细胞抗原（HLA）I类分子下调，这是病毒感染和肿瘤转化的一个重要标志。KIR基因和HLA基因位于不同的染色体上，KIR与HLA I类分子的相互作用代表了遗传上位性的一个例子，即受体/配体对的存在是诱导功能活性所必需的，而一方存在而另一方缺失则不足以影响NK细胞功能。由于HLA I类分子和KIR基因的高度变异性，KIR/ KIR配体（KIR-L）的相互作用极其多样。KIR多态性源于单倍型和等位基因变异，并受到自然选择的影响。KIR变异性影响NK细胞的发育，进而影响KIR库、KIR表达、KIR/ KIR-L相互作用的强度以及传递信号的能力。此外，它可能会影响感染、自身免疫性疾病、妊娠和同种异体移植过程中的NK细胞功能。本综述总结了KIR/ KIR-L相互作用的遗传和功能特征，并概述了它们在临床研究中的潜在相关性。
