Stem Cell Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Int Immunopharmacol. 2021 Mar;92:107361. doi: 10.1016/j.intimp.2020.107361. Epub 2021 Jan 8.
Natural killer (NK) cells are essential for the elimination of the transformed and cancerous cells. Killer cell immunoglobulin-like receptors (KIRs) which expressed by T and NK cells, are key regulator of NK cell function. The KIR and their ligands, MHC class I (HLA-A, B and C) molecules, are highly polymorphic and their related genes are located on 19 q13.4 and 6 q21.3 chromosomes, respectively. It is clear that particular interaction between the KIRs and their related ligands can influence on the prevalence, progression and outcome of several diseases, like complications of pregnancy, viral infection, autoimmune diseases, and hematological malignancies. The mechanisms of immune signaling in particular NK cells involvement in causing pathological conditions are not completely understood yet. Therefore, better understanding of the molecular mechanism of KIR-MHC class I interaction could facilitate the treatment strategy of diseases. The present review focused on the main characteristics and functional details of various KIR and their combination with related ligands in diseases and also highlights ongoing efforts to manipulate the key checkpoints in NK cell-based immunotherapy.
自然杀伤 (NK) 细胞对于消除转化和癌变细胞至关重要。表达在 T 和 NK 细胞上的杀伤细胞免疫球蛋白样受体 (KIR) 是 NK 细胞功能的关键调节剂。KIR 及其配体，MHC Ⅰ类 (HLA-A、B 和 C) 分子，高度多态性，其相关基因分别位于 19q13.4 和 6q21.3 染色体上。显然，KIR 与相关配体之间的特定相互作用会影响多种疾病的流行、进展和结果，如妊娠并发症、病毒感染、自身免疫性疾病和血液恶性肿瘤。特定 NK 细胞参与引起病理状况的免疫信号传导机制尚未完全理解。因此，更好地了解 KIR-MHC Ⅰ类相互作用的分子机制可以促进疾病的治疗策略。本综述重点介绍了各种 KIR 的主要特征和功能细节及其与相关配体在疾病中的结合，并强调了目前在操纵 NK 细胞为基础的免疫治疗中的关键检查点方面所做的努力。
