T cell immunoreceptor with Ig and ITIM domains (TIGIT), also called WUCAM, VSIG9 and Vstm3, is a member of the CD28 family within the Ig superfamily of proteins. TIGIT contains an immunoglobulin variable domain, a transmembrane domain and an immunoreceptor tyrosine-based inhibitory motif (ITIM), and is expressed on regulatory, memory, activated T cells and NK cells. TIGIT binds to CD155(PVR) that appear on dendritic cells (DC), macrophages and endothelium with high affinity, and CD112(PVRL2) with lower affinity, but not CD113 (PVRL3). TIGIT-Fc fusion protein could interact with PVR on DC and enhance the secretion of IL-10, but inhibit the macrophage activation. Mice lacking TIGIT show increased T cell responses and susceptibility to autoimmune challenges, while knockdown of TIGIT with siRNA in human memory T cells did not affect T cell responses.
