CDB20:0002951 TIGIT — PVR
Experimentally validated in Human, Mouse; Orthology-inferred in Human, Rat, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep, Mouse, Zebrafish
Title
Journal:; Year Published:
Abstract
The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells.
Nature immunology, 2009; PubMed, Homo sapiens TIGIT — Homo sapiens PVR
ABSTRACT: Here we have identified a surface protein, TIGIT, containing an immunoglobulin variable domain, a transmembrane domain and an immunoreceptor tyrosine-based inhibitory motif that was expressed on regulatory, memory and activated T cells. Poliovirus receptor, which is expressed on dendritic cells, bound TIGIT with high affinity. A TIGIT-Fc fusion protein inhibited T cell activation in vitro, and this was dependent on the presence of dendritic cells. The binding of poliovirus receptor to TIGIT on human dendritic cells enhanced the production of interleukin 10 and diminished the production of interleukin 12p40. Knockdown of TIGIT with small interfering RNA in human memory T cells did not affect T cell responses. TIGIT-Fc inhibited delayed-type hypersensitivity reactions in wild-type but not interleukin 10-deficient mice. Our data suggest that TIGIT exerts immunosuppressive effects by binding to poliovirus receptor and modulating cytokine production by dendritic cells.
The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity.
Proceedings of the National Academy of Sciences of the United States of America, 2009; PubMed, Homo sapiens TIGIT — Homo sapiens PVR
ABSTRACT: NK cell cytotoxicity is controlled by numerous NK inhibitory and activating receptors. Most of the inhibitory receptors bind MHC class I proteins and are expressed in a variegated fashion. It was recently shown that TIGIT, a new protein expressed by T and NK cells binds to PVR and PVR-like receptors and inhibits T cell activity indirectly through the manipulation of DC activity. Here, we show that TIGIT is expressed by all human NK cells, that it binds PVR and PVRL2 but not PVRL3 and that it inhibits NK cytotoxicity directly through its ITIM. Finally, we show that TIGIT counter inhibits the NK-mediated killing of tumor cells and protects normal cells from NK-mediated cytotoxicity thus providing an "alternative self" mechanism for MHC class I inhibition.