CDB20:0002885 PVR — TIGIT
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 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 PVR — Homo sapiens TIGIT
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.
The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions.
Nature immunology, 2014; PubMed, Mus Musculus Pvr — Mus Musculus Tigit
ABSTRACT: CD96, CD226 (DNAM-1) and TIGIT belong to an emerging family of receptors that interact with nectin and nectin-like proteins. CD226 activates natural killer (NK) cell-mediated cytotoxicity, whereas TIGIT reportedly counterbalances CD226. In contrast, the role of CD96, which shares the ligand CD155 with CD226 and TIGIT, has remained unclear. In this study we found that CD96 competed with CD226 for CD155 binding and limited NK cell function by direct inhibition. As a result, Cd96(-/-) mice displayed hyperinflammatory responses to the bacterial product lipopolysaccharide (LPS) and resistance to carcinogenesis and experimental lung metastases. Our data provide the first description, to our knowledge, of the ability of CD96 to negatively control cytokine responses by NK cells. Blocking CD96 may have applications in pathologies in which NK cells are important.