The mechanisms controlling the recognition of tumor- and virus-infected cells by NKp46
| Autor: | Marianna Lev, Gil Katz, Tal I. Arnon, Aviva Joseph, Niva Lieberman, Eli Kedar, Noga Bloushtain, Ofer Mandelboim, Hagit Achdout, Angel Porgador, Tsufit Gonen-Gross, Ahuva Bar-Ilan, Roi Gazit |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Viral Hemagglutinin Lysis Recombinant Fusion Proteins Immunology Hemagglutinin (influenza) Enzyme-Linked Immunosorbent Assay Biochemistry Sendai virus Virus chemistry.chemical_compound Mice Dual role Tumor Cells Cultured Animals Antigens Ly Humans Receptors Immunologic Receptor Cell Line Transformed Binding Sites Membrane Glycoproteins biology Natural Cytotoxicity Triggering Receptor 1 Antibodies Monoclonal Cell Biology Hematology Virology Cell biology Sialic acid Killer Cells Natural chemistry Virus Diseases biology.protein |
| DOI: | 10.1182/blood-2003-05-1716 |
| Popis: | 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 α2,6-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. |
| Databáze: | OpenAIRE |
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