Parham Peter
Department of Structural Biology, Stanford University, Stanford CA 94305, USA.
Immunol Rev. 2006 Dec;214:155-60. doi: 10.1111/j.1600-065X.2006.00462.x.
Combining population analysis with in-depth analysis of selected individuals, the tolerance of human natural killer (NK) cells to autologous major histocompatibility complex (MHC) class I and potential reactivity to allogeneic MHC class I have been studied. Analysis of NK cell clones in long-term culture and peripheral blood NK cells after short-term culture (20-24 h) shows that NK cell tolerance is determined by interactions of autologous MHC class I with CD94:NKG2A and inhibitory killer cell immunoglobulin-like receptors (KIRs). Alloreactivity is predicted whenever the donor of the allogeneic target lacks a cognate MHC class I-KIR, ligand-receptor pair that is present in the NK cell donor. In the human population, there is a wide variation in the NK cell repertoire of KIRs and CD94:NKG2A expression. Variation is principally due to KIR gene variation and polymorphism, with a smaller effect due to MHC class I. The presence of MHC class I increases the frequency of NK cells expressing the cognate KIR, an effect that is diminished by the presence of other cognate-ligand pairs. The minor influence of MHC class I on the KIR repertoire indicates that NK cell development is an efficient process in which the expression of inhibitory MHC class I receptors at the final stages ensures that functionally active human NK cells are self-tolerant.
通过将群体分析与对选定个体的深入分析相结合，研究了人类自然杀伤（NK）细胞对自身主要组织相容性复合体（MHC）I类分子的耐受性以及对异体MHC I类分子的潜在反应性。对长期培养的NK细胞克隆和短期培养（20 - 24小时）后的外周血NK细胞进行分析表明，NK细胞的耐受性由自身MHC I类分子与CD94:NKG2A以及抑制性杀伤细胞免疫球蛋白样受体（KIRs）之间的相互作用决定。只要异体靶细胞的供体缺乏NK细胞供体中存在的同源MHC I - KIR配体 - 受体对，就可预测到异体反应性。在人类群体中，KIRs的NK细胞库和CD94:NKG2A表达存在广泛差异。这种差异主要归因于KIR基因变异和多态性，MHC I类分子的影响较小。MHC I类分子的存在增加了表达同源KIR的NK细胞频率，而其他同源配体对的存在会减弱这种效应。MHC I类分子对KIR库的影响较小，这表明NK细胞的发育是一个高效的过程，其中在最终阶段抑制性MHC I类受体的表达确保了功能活跃的人类NK细胞具有自身耐受性。
