The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity
Noa Stanietsky, Hrvoje Šimić, Jurica Arapović, Amir Toporik, Ofer Levy, Amit Novik, Zurit Levine, Meirav Beiman, Liat Dassa, Hagit Achdout, Noam Stern‐Ginossar, Pinhas Tsukerman, Stipan Jonjić, Ofer Mandelboim
Proceedings of the National Academy of Sciences · 2009 · 3,563 citationsOpen access
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.
Cite this paper
Stanietsky, N., Šimić, H., Arapović, J., Toporik, A., Levy, O., Novik, A., Levine, Z., Beiman, M., Dassa, L., Achdout, H., Stern‐Ginossar, N., Tsukerman, P., Jonjić, S., & Mandelboim, O. (2009). The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proceedings of the National Academy of Sciences, 106(42), 17858–17863. https://doi.org/10.1073/pnas.0903474106
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