title: The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity.
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.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, IMRIC, Hadassah Medical School, Hebrew University, Jerusalem 91120, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Stanietsky
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Simic
authors.forename: Jurica
authors.initials: J
authors.lastname: Arapovic
authors.forename: Amir
authors.initials: A
authors.lastname: Toporik
authors.forename: Ofer
authors.initials: O
authors.lastname: Levy
authors.forename: Amit
authors.initials: A
authors.lastname: Novik
authors.forename: Zurit
authors.initials: Z
authors.lastname: Levine
authors.forename: Meirav
authors.initials: M
authors.lastname: Beiman
authors.forename: Liat
authors.initials: L
authors.lastname: Dassa
authors.forename: Hagit
authors.initials: H
authors.lastname: Achdout
authors.forename: Noam
authors.initials: N
authors.lastname: Stern-Ginossar
authors.forename: Pinhas
authors.initials: P
authors.lastname: Tsukerman
authors.forename: Stipan
authors.initials: S
authors.lastname: Jonjic
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D053646:Interleukin-2 Receptor beta Subunit / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008024:Ligands; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D051379:Mice; D000075983:Nectins; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; C508020:IL2RB protein, human; D053646:Interleukin-2 Receptor beta Subunit; D008024:Ligands; C000619014:NECTIN3 protein, human; C000619016:Nectin2 protein, mouse; C000619017:Nectin3 protein, mouse; D000075983:Nectins; D011971:Receptors, Immunologic; D011991:Receptors, Virus; D011994:Recombinant Proteins; C534712:TIGIT protein, human; C066100:poliovirus receptor