Contribution of inhibitory receptor TIGIT to NK cell education

Publication date: Available online 21 April 2017
Source:Journal of Autoimmunity
Author(s): Yuke He, Hui Peng, Rui Sun, Haiming Wei, Hans-Gustaf Ljunggren, Wayne M. Yokoyama, Zhigang Tian
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.

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