The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity.
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.
Stanietsky
Noa
N
The Lautenberg Center for General and Tumor Immunology, IMRIC, Hadassah Medical School, Hebrew University, Jerusalem 91120, Israel.
Simic
Hrvoje
H
Arapovic
Jurica
J
Toporik
Amir
A
Levy
Ofer
O
Novik
Amit
A
Levine
Zurit
Z
Beiman
Meirav
M
Dassa
Liat
L
Achdout
Hagit
H
Stern-Ginossar
Noam
N
Tsukerman
Pinhas
P
Jonjic
Stipan
S
Mandelboim
Ofer
O
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
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