T cell immunoreceptor with Ig and ITIM domains (TIGIT), also known as V-set and transmembrane domain-containing protein 3 (Vstm3), is a 26 kD, type I transmembrane protein and member of the CD28 family. TIGIT is expressed on activated T cells, follicular T helper, memory, and regulatory T cells as well as on NK cells. Its ligands are PVR, PVRL2, PVRL3, CD155, and CD112. TIGIT is a negative regulator of NK and T cell activation. Engagement of TIGIT by dendritic cells results in their differentiation into a tolerogenic phenotype, with an increased secretion of IL-10 and a diminished production of IL-12. Mice deficient for TIGIT are more susceptible to autoimmune disease.