Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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 hemagglutinin-neuroaminidase 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 alpha2,6-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.

Original publication

DOI

10.1182/blood-2003-05-1716

Type

Journal article

Journal

Blood

Publication Date

15/01/2004

Volume

103

Pages

664 - 672

Keywords

Animals, Antibodies, Monoclonal, Antigens, Ly, Binding Sites, Cell Line, Transformed, Enzyme-Linked Immunosorbent Assay, Humans, Killer Cells, Natural, Male, Membrane Glycoproteins, Mice, Natural Cytotoxicity Triggering Receptor 1, Receptors, Immunologic, Recombinant Fusion Proteins, Sendai virus, Tumor Cells, Cultured, Virus Diseases