Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 42, Pages 17858-17863Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0903474106
Keywords
inhibitory receptors; natural killers
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Funding
- U.S.-Israel Binational Science Foundation
- Israeli Cancer Research Foundation
- The Israeli Science Foundation (ISF)
- European Consortium [MRTN-CT-2005, LSCH-CT-2005-518178]
- Association for International Cancer Research
- ISF (Morasha)
- Israel-Croatia Research Grant
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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.
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