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      The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans

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          Abstract

          Cancer development is often associated with the lack of specific and efficient recognition of tumor cells by the immune system. Natural killer (NK) cells are lymphocytes of the innate immune system that participate in the elimination of tumors. We report the identification of a tumor cell surface molecule that binds NKp30, a human receptor which triggers antitumor NK cell cytotoxicity and cytokine secretion. This previously unannotated gene belongs to the B7 family and, hence, was designated B7-H6. B7-H6 triggers NKp30-mediated activation of human NK cells. B7-H6 was not detected in normal human tissues but was expressed on human tumor cells, emphasizing that the expression of stress-induced self-molecules associated with cell transformation serves as a mode of cell recognition in innate immunity.

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          Most cited references26

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          NK cell recognition.

          The integrated processing of signals transduced by activating and inhibitory cell surface receptors regulates NK cell effector functions. Here, I review the structure, function, and ligand specificity of the receptors responsible for NK cell recognition.
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            Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy.

            Metazoan organisms may discriminate between self and non-self not only by the presence of foreign antigens but also by the absence of normal self markers. Mammalian adaptive immune responses use the first strategy, with the additional requirement that foreign antigens are recognized in the context of self-major histocompatibility complex (MHC) products at the cell surface. Aberrant cells which fail to express MHC products adequately can therefore avoid detection. A more primitive but complementary defence system, eliminating such cells on the basis of absent self-markers, is suggested by a re-interpretation of phenomena associated with metastasis and natural resistance. We now show that murine lymphoma cells selected for loss of H-2 expression are less malignant after low-dose inoculation in syngeneic hosts than are wild-type cells, and that the rejection of such cells is non-adaptive. On the basis of our data, we suggest that natural killer cells are effector cells in a defence system geared to detect the deleted or reduced expression of self-MHC.
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              Roles of the NKG2D immunoreceptor and its ligands.

              According to present concepts, innate immunity is regulated by receptors that determine danger levels by responding to molecules that are associated with infection or cellular distress. NKG2D is, perhaps, the best characterized receptor that is associated with responses to cellular distress, defined as transformation, infection or cell stress. This review summarizes recent findings that concern NKG2D, its ligands, its signalling properties and its role in disease, and provides a framework for considering how the induction of immune responses can be regulated by cellular responses to injury.
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                Author and article information

                Journal
                J Exp Med
                J. Exp. Med
                jem
                The Journal of Experimental Medicine
                The Rockefeller University Press
                0022-1007
                1540-9538
                6 July 2009
                : 206
                : 7
                : 1495-1503
                Affiliations
                [1 ]Molecular and Cell Based Discovery , [2 ]Protein Biochemistry , [3 ]Bioinformatics , and [4 ]Autoimmunity and Inflammation, ZymoGenetics Inc., Seattle, WA 98102
                [5 ]Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Campus de Luminy, Marseille 13288, France
                [6 ]Institut National de la Santé et de la Recherche Médicale UMR 631, Marseille 13288, France
                [7 ]Centre National de la Recherche Scientifique UMR6102, Marseille 13288, France
                [8 ]Institut Paoli-Calmettes, Centre de Ressources Biologiques en Oncologie, Marseille 13009, France
                [9 ]Centre de Recherches en Cancérologie de Marseille, Institut National de la Santé et de la Recherche Médicale UMR 891, Marseille 13009, France
                [10 ]Dipartimento di Medicina Sperimentale e Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, Genova 16132, Italy
                [11 ]Hôpital de la Conception, Assistance Publique - Hôpitaux de Marseille, Marseille 13005, France
                Author notes
                CORRESPONDENCE Steven D. Levin: levins@ 123456zgi.com OR Eric Vivier: vivier@ 123456ciml.univ-mrs.fr
                Article
                20090681
                10.1084/jem.20090681
                2715080
                19528259
                ec1c1d81-22ae-4896-a633-685f0d04ff83
                © 2009 Brandt et al.

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

                History
                : 25 March 2009
                : 21 May 2009
                Categories
                Brief Definitive Report

                Medicine
                Medicine

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