Contribution of inhibitory receptor TIGIT to NK cell education

• Published in: Journal of autoimmunity Vol. 81; pp. 1 - 12
• Main Authors: He, Yuke, Peng, Hui, Sun, Rui, Wei, Haiming, Ljunggren, Hans-Gustaf, Yokoyama, Wayne M, Tian, Zhigang
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2017
• Subjects: Allergy and Immunology; Animals; Antigens, Differentiation, T-Lymphocyte - metabolism; Biomarkers; CD155; Cytotoxicity, Immunologic - genetics; Cytotoxicity, Immunologic - immunology; Education; Gene Expression; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Licensing; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Medicin och hälsovetenskap; MHC-I; Mice; Mice, Knockout; NK cells; Protein Binding; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Receptors, Virus - genetics; Receptors, Virus - metabolism; Signal Transduction; TIGIT; NK cells; MHC-I; Licensing; TIGIT; Education; CD155
• ISSN: 0896-8411; 1095-9157; 1095-9157
• DOI: 10.1016/j.jaut.2017.04.001

Abstract 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.