Balancing natural killer cell activation through paired receptors

Natural killer (NK) cells are innate lymphocytes that are crucial for the control of infections and malignancies. NK cells express a variety of inhibitory and activating receptors that facilitate fine discrimination between damaged and healthy cells. Among them, a family of molecules that bind nectin and nectin-like proteins has recently emerged and has been shown to function as an important regulator of NK cell functions. These molecules include CD226, T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT), CD96, and cytotoxic and regulatory T cell molecule (CRTAM). In this Review, we focus on the recent advances in our understanding of how these receptors regulate NK cell biology and of their roles in pathologies such as cancer, infection and autoimmunity.