Fig. 1.

Diagram of CD155/CD112-mediated immunoregulatory pathway on NK cells. Interaction between TIGIT and CD155/CD112 induces inhibition of NK cell function via the phosphorylation of the ITIM domain and recruitment of SHIP1. This, in turn, inhibits MAPK, PI3K, and NF-κβ signaling. Interaction between DNAM-1/CD96 and CD155/CD112 provides an activating stimulus to NK cells. Upon binding, DNAM-1 relocates to lipid rafts where it homodimerizes and crosslinks with LFA-1 receptors. These cause phosphorylation of the Tyr³²² residue of DNAM-1 resulting in NK cell cytolytic activity, cytokine secretion, and degranulation