Contribution of inhibitory receptor TIGIT to NK cell education

Yuke He, Hui Peng, Rui Sun, Haiming Wei, Hans Gustaf Ljunggren, Wayne M. Yokoyama, Zhigang Tian

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalJournal of Autoimmunity
Volume81
DOIs
StatePublished - Jul 2017

Keywords

  • CD155
  • Education
  • Licensing
  • MHC-I
  • NK cells
  • TIGIT

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