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Blood, 15 January 2004, Vol. 103, No. 2, pp. 664-672. Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-05-1716. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1716v1 103/2/664    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Arnon, T. I. Articles by Mandelboim, O. Search for Related Content PubMed PubMed Citation Articles by Arnon, T. I. Articles by Mandelboim, O. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY The mechanisms controlling the recognition of tumor- and virus-infected cells by NKp46 Tal I. Arnon, Hagit Achdout, Niva Lieberman, Roi Gazit, Tsufit Gonen-Gross, Gil Katz, Ahuva Bar-Ilan, Noga Bloushtain, Marianna Lev, Aviva Joseph, Eli Kedar, Angel Porgador, and Ofer Mandelboim From The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem, Israel; the Department of Microbiology and Immunology, Faculty of Health Sciences, and the Cancer Research Center, Ben-Gurion University of the Negev, Beer Sheva, Israel. The destruction of viral-infected and tumor cells is mediated in part via the lysis receptor of natural killer (NK) cells, NKp46. The nature, however, of its lysis ligands expressed on target cells is poorly defined. Recently, we have identified a novel functional interaction between the lysis receptors NKp46 and NKp44 and the hemagglutinin of influenza and hemgglutininneuroaminidase of Sendai viruses. This recognition depends on the sialylation of NKp46 and NKp44 receptors. In this study, we expand the significance of these observations by demonstrating a conserved pattern of NKp46 and NKp44 recognition by various hemagglutinins derived from different viral strains. We further establish that this recognition is direct and mainly mediated via 2,6-linked sialic acid carried by NKp46. In addition, we demonstrate that the ability of NKp46 to recognize target cells is confined to the membrane proximal domain, and largely relies on the highly conserved sugar-carrying residue, Thr 225. This residue plays a critical dual role in NKp46 interactions with both viral hemagglutinins and the unknown tumor ligands via different mechanisms. These results may explain the ability of NK cells to kill such a broad spectrum of viral-infected and tumor cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. L. Heltzer, S. E. Coffin, K. Maurer, A. Bagashev, Z. Zhang, J. S. Orange, and K. E. Sullivan Immune dysregulation in severe influenza J. Leukoc. Biol., June 1, 2009; 85(6): 1036 - 1043. [Abstract] [Full Text] [PDF] X. Wang, A. Ottosson, C. Ji, X. Feng, M. Nordenskjold, J.-I. Henter, B. Fadeel, and C. Zheng Proteasome inhibition induces apoptosis in primary human natural killer cells and suppresses NKp46-mediated cytotoxicity Haematologica, April 1, 2009; 94(4): 470 - 478. [Abstract] [Full Text] [PDF] G. G. Halfteck, M. Elboim, C. Gur, H. Achdout, H. Ghadially, and O. Mandelboim Enhanced In Vivo Growth of Lymphoma Tumors in the Absence of the NK-Activating Receptor NKp46/NCR1 J. Immunol., February 15, 2009; 182(4): 2221 - 2230. 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Thompson, L. J. Phillipson, C. Thompson, E. Taylor, M. Zambon, H. M. I. Osborn, W. S. Barclay, and P. Borrow Alterations in Receptor Binding Properties of Recent Human Influenza H3N2 Viruses Are Associated with Reduced Natural Killer Cell Lysis of Infected Cells J. Virol., October 15, 2007; 81(20): 11170 - 11178. [Abstract] [Full Text] [PDF] P. Roda-Navarro and H. T. Reyburn Intercellular protein transfer at the NK cell immune synapse: mechanisms and physiological significance FASEB J, June 1, 2007; 21(8): 1636 - 1646. [Abstract] [Full Text] [PDF] E. Estefania, R. Flores, N. Gomez-Lozano, H. Aguilar, M. Lopez-Botet, and C. Vilches Human KIR2DL5 Is an Inhibitory Receptor Expressed on the Surface of NK and T Lymphocyte Subsets J. Immunol., April 1, 2007; 178(7): 4402 - 4410. [Abstract] [Full Text] [PDF] M. Draghi, A. Pashine, B. Sanjanwala, K. Gendzekhadze, C. Cantoni, D. Cosman, A. Moretta, N. M. Valiante, and P. 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