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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.

SUBMITTER: Stanietsky N

PROVIDER: S-EPMC2764881 | biostudies-other | 2009 Oct

REPOSITORIES: biostudies-other

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The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity.

Stanietsky Noa N 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

Proceedings of the National Academy of Sciences of the United States of America 20091007 42

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 inh ...[more]

PMID: 19815499

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Mouse TIGIT inhibits NK-cell cytotoxicity upon interaction with PVR.

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