Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, VIC, Australia.
Immunol Rev. 2015 Sep;267(1):148-66. doi: 10.1111/imr.12319.
The surveillance of target cells by natural killer (NK) cells utilizes an ensemble of inhibitory and activating receptors, many of which interact with major histocompatibility complex (MHC) class I molecules. NK cell recognition of MHC class I proteins is important developmentally for the acquisition of full NK cell effector capacity and during target cell recognition, where the engagement of inhibitory receptors and MHC class I molecules attenuates NK cell activation. Human NK cells have evolved two broad strategies for recognition of human leukocyte antigen (HLA) class I molecules: (i) direct recognition of polymorphic classical HLA class I proteins by diverse receptor families such as the killer cell immunoglobulin-like receptors (KIRs), and (ii) indirect recognition of conserved sets of HLA class I-derived peptides displayed on the non-classical HLA-E for recognition by CD94-NKG2 receptors. In this review, we assess the structural basis for the interaction between these NK receptors and their HLA class I ligands and, using the suite of published KIR and CD94-NKG2 ternary complexes, highlight the features that allow NK cells to orchestrate the recognition of a range of different HLA class I proteins.
自然杀伤 (NK) 细胞通过一系列抑制性和激活性受体来监测靶细胞，其中许多受体与主要组织相容性复合体 (MHC) Ⅰ类分子相互作用。NK 细胞对 MHC Ⅰ类蛋白的识别对于获得完全的 NK 细胞效应功能以及在靶细胞识别过程中是重要的，在此过程中，抑制性受体和 MHC Ⅰ类分子的结合会减弱 NK 细胞的激活。人类 NK 细胞已经进化出两种识别人类白细胞抗原 (HLA) Ⅰ类分子的广泛策略：(i) 通过不同的受体家族（如杀伤细胞免疫球蛋白样受体 (KIR)）直接识别多态性经典 HLA Ⅰ类蛋白，以及 (ii) 通过非经典 HLA-E 上展示的保守 HLA Ⅰ类衍生肽间接识别，由 CD94-NKG2 受体识别。在这篇综述中，我们评估了这些 NK 受体与其 HLA Ⅰ类配体相互作用的结构基础，并使用已发表的一系列 KIR 和 CD94-NKG2 三元复合物，突出了允许 NK 细胞协调识别一系列不同 HLA Ⅰ类蛋白的特征。
