Stanietsky Noa, Simic Hrvoje, Arapovic Jurica, Toporik Amir, Levy Ofer, Novik Amit, Levine Zurit, Beiman Meirav, Dassa Liat, Achdout Hagit, Stern-Ginossar Noam, Tsukerman Pinhas, Jonjic Stipan, Mandelboim Ofer
The Lautenberg Center for General and Tumor Immunology, IMRIC, Hadassah Medical School, Hebrew University, Jerusalem 91120, Israel.
Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17858-63. doi: 10.1073/pnas.0903474106. Epub 2009 Oct 7.
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.
自然杀伤（NK）细胞的细胞毒性受多种NK抑制性和激活性受体的调控。大多数抑制性受体与MHC I类蛋白结合，并以斑驳的方式表达。最近研究表明，TIGIT是一种由T细胞和NK细胞表达的新蛋白，它与脊髓灰质炎病毒受体（PVR）和PVR样受体结合，并通过操纵树突状细胞（DC）的活性间接抑制T细胞活性。在此，我们发现所有人类NK细胞均表达TIGIT，它能结合PVR和PVRL2，但不结合PVRL3，并且它通过其免疫受体酪氨酸抑制基序（ITIM）直接抑制NK细胞的细胞毒性。最后，我们表明TIGIT可对抗抑制NK介导的肿瘤细胞杀伤，并保护正常细胞免受NK介导的细胞毒性作用，从而为MHC I类抑制提供一种“替代性自身”机制。
