Fig. 3

The interaction of TIGIT-related ligands and receptors. PVRL4, CD155, CD112, and CD113 are expressed on tumor cells or APCs as ligands, and CD226, TIGIT, CD96, and CD112R act as receptors on T cells or NK cells. Every receptor here, apart from CD226 which uniquely possesses an ITT-like domain, features an intracellular ITIM domain. TIGIT has an ITT-like motif, and CD96 contains a YXXM motif. TIGIT binds to CD155 with a higher affinity and inhibits the interaction of CD226 and CD155. In humans, the inhibition of TIGIT mainly relies on the phosphorylation of an ITT-like motif and ultimately terminates PI3K/MAPK signaling. However, the downstream function of CD96 has not been clear until now. The arrow’s thickness represents the affinity of ligands and receptors