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

Noa Stanietsky, Hrvoje Simic, Jurica Arapovic, Amir Toporik, Ofer Levy, Amit Novik, Zurit Levine, Meirav Beiman, Liat Dassa, Hagit Achdout, Noam Stern-Ginossar, Pinhas Tsukerman, Stipan Jonjic*, Ofer Mandelboim

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

628 Scopus citations

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 cytoxicity thus providing an "alternative self" mechanism for MHC class I inhibition.

Original languageAmerican English
Pages (from-to)17858-17863
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number42
DOIs
StatePublished - 20 Oct 2009

Keywords

  • Inhibitory receptors
  • Natural killers

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