Institute of Immunology, Key Laboratory of Innate Immunity and Chronic Disease of Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, 230027, China.
Institute of Immunology, Key Laboratory of Innate Immunity and Chronic Disease of Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, 230027, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
J Autoimmun. 2017 Jul;81:1-12. doi: 10.1016/j.jaut.2017.04.001. Epub 2017 Apr 21.
Engagement of inhibitory receptors by cognate host MHC-I molecules triggers NK cell education, resulting in functional maturation and allowing NK cells to sense missing-self. However, NK cells also express inhibitory receptors for non-MHC-I ligands and their role in NK cell education is poorly understood. TIGIT is a recently identified inhibitory receptor that recognizes a non-MHC-I ligand CD155. Here, we demonstrated that TIGIT NK cells from wild-type mice exerted augmented responsiveness to various stimuli, including targets that lacked expression of CD155 ligand. TIGIT NK cells derived from CD155-deficient hosts, however, exhibited functional impairment, indicating that the engagement of TIGIT receptor by host CD155 promoted NK cell functional maturation. Furthermore, TIGIT deficiency impaired NK cell-mediated missing-self recognition and rejection of CD155 targets, such as allogenic splenocytes and certain tumor cells, in an MHC-I-independent and CD226-unrelated manner. Thus, TIGIT-CD155 pathway is also involved in the acquisition of optimal NK cell effector function, representing a novel MHC-I-independent education mechanism for NK cell tolerance and activation.
抑制性受体与同源宿主 MHC-I 分子的结合触发 NK 细胞的教育，导致功能成熟，并使 NK 细胞能够感知自身缺失。然而，NK 细胞也表达非 MHC-I 配体的抑制性受体，其在 NK 细胞教育中的作用尚不清楚。TIGIT 是一种新鉴定的抑制性受体，它识别非 MHC-I 配体 CD155。在这里，我们证明了来自野生型小鼠的 TIGIT NK 细胞对各种刺激表现出增强的反应性，包括缺乏 CD155 配体表达的靶标。然而，来自 CD155 缺陷型宿主的 TIGIT NK 细胞表现出功能障碍，表明宿主 CD155 结合 TIGIT 受体促进了 NK 细胞的功能成熟。此外，TIGIT 缺陷以 MHC-I 非依赖性和 CD226 无关的方式损害了 NK 细胞介导的自身缺失识别和对 CD155 靶标的排斥，如同种异体脾细胞和某些肿瘤细胞。因此，TIGIT-CD155 途径也参与了获得最佳 NK 细胞效应功能，代表了一种新的 MHC-I 非依赖性 NK 细胞耐受和激活的教育机制。
