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

doi:10.1073/pnas.0903474106

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

Department of Immunology and Cancer Research

Research output: Contribution to journal › Article › peer-review

662 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 language	English
Pages (from-to)	17858-17863
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	106
Issue number	42
DOIs	https://doi.org/10.1073/pnas.0903474106
State	Published - 20 Oct 2009

Keywords

Inhibitory receptors
Natural killers

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1073/pnas.0903474106

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Stanietsky, N., Simic, H., Arapovic, J., Toporik, A., Levy, O., Novik, A., Levine, Z., Beiman, M., Dassa, L., Achdout, H., Stern-Ginossar, N., Tsukerman, P., Jonjic, S., & Mandelboim, O. (2009). The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proceedings of the National Academy of Sciences of the United States of America, 106(42), 17858-17863. https://doi.org/10.1073/pnas.0903474106

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Stanietsky, N, Simic, H, Arapovic, J, Toporik, A, Levy, O, Novik, A, Levine, Z, Beiman, M, Dassa, L, Achdout, H, Stern-Ginossar, N, Tsukerman, P, Jonjic, S & Mandelboim, O 2009, 'The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 42, pp. 17858-17863. https://doi.org/10.1073/pnas.0903474106

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AU - Stanietsky, Noa

AU - Simic, Hrvoje

AU - Arapovic, Jurica

AU - Toporik, Amir

AU - Levy, Ofer

AU - Novik, Amit

AU - Levine, Zurit

AU - Beiman, Meirav

AU - Dassa, Liat

AU - Achdout, Hagit

AU - Stern-Ginossar, Noam

AU - Tsukerman, Pinhas

AU - Jonjic, Stipan

AU - Mandelboim, Ofer

PY - 2009/10/20

Y1 - 2009/10/20

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

Abstract

Keywords

UN SDGs

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