Figure 1.

Interactions of T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT) and CD226 with nectin and nectin-like molecules. TIGIT and CD226 are mainly expressed on T and natural killer (NK) cells. TIGIT has multiple ligands, including poliovirus receptor (PVR), nectin-2, nectin-3, and nectin-4. TIGIT binds to nectin-2 and nectin-3 with lower affinity than PVR. Upon engagement, TIGIT transmits inhibitory signals through ITIM and immunoglobulin tyrosine tail (ITT)-like motifs in its cytoplasmic domain. CD226 interacts with PVR and nectin-2 to deliver a positive signal. TIGIT binds to PVR with higher affinity than CD226. The integrated signals formed by their complex interactions regulate immune-cell functions, which is important for immunity and inflammatory responses. Interactions between receptors and ligands are depicted by two-sided arrows. The arrows are proportional to the reported affinities of the interactions except nectin-4.