TIGIT (human)-muIg Fusion Protein

TIGIT (T cell immunoreceptor with Ig and ITIM domains) is a novel member of the immunoglobulin super family (IgSF). TIGIT and CD226 bind the same ligands, the two nectin-family members poliovirus receptor (PVR) and poliovirus receptor-related 2 (CD112) and compete for each other. TIGIT inhibits while CD226 activates the signaling through PVR and CD112. TIGIT and CD226 directly interact at the cell surface and this interaction impairs CD226 homodimerization and function. TIGIT is absent on naive T cells, but is expressed on activated Tregs and memory T cells, and on NK cells and NKT cells. TIGIT negatively regulates T cell activation and blockade of TIGIT exacerbates several immune diseases. TIGIT also activates the PVR receptor on dendritic cells (DCs). Addition of TIGIT (human):Fc (human) to DCs triggers phosphorylation of PVR and elicits downstream signaling, which then inhibits T cell responses by producing IL-10. TIGIT also negatively regulates NK cell cytotoxicity and cytokine production. TIGIT is directly regulated by FoxP3 and promotes inducible Treg differentiation.