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Description

T-cell immunoreceptor with Ig and ITIM domains (UniProt: P86176, also known as V-set and immunoglobulin domain-containing protein 9, TIGIT) is encoded by the Tigit (also known as Vstm3) gene (Gene ID: 100043314) in murine species. TIGIT is a single-pass type I, homodimeric, membrane protein that is synthesized with a signal peptide (aa 1-28), which is subsequently cleaved off to generate the mature form that contains an extracellular domain (aa 29-148), a transmembrane domain (aa 149-169), and a cytoplasmic domain (aa 170-249). The cytoplasmic domain contains an immunoreceptor tyrosine-based inhibitor motif (ITIM, aa 234-239), which is involved in the modulation of its cellular responses. It serves as a coinhibitory receptors with CD226 and is expressed on NK cells, activated T cells, memory T cells, and a subset of regulatory T cells and blocks immune responses by affecting T cells and APCs. It is shown to bind to poliovirus receptor (PVR) with high affinity to form a heterotetrameric assembly of two TIGIT and two PVR molecules. This causes increased secretion of IL-10 and decreased secretion of IL-12B and suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells. TIGIT also serves as a functional ligand and induces dendritic cells to acquire a tolerogenic phenotype via ligation of PVR. TIGIT -/- mice, when challenged, develop severe experimental autoimmune encephalomyelitis compared to wild-type mice. Loss of TIGIT also in mice also results in hyperproliferative T cell responses and increased susceptibility to autoimmunity. (Ref.: Dixon, KO., et al. (2018). J. Immunol. 200(8), 3000-3007, Joller, N., et al. (2011). J. Immunol. 186(3), 1338-1342).