Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells

Ofer Mandelboim, Niva Lieberman, Marianna Lev, Lada Paul, Tal I. Arnon, Yuri Bushkin, Daniel M. Davis, Jack L. Strominger, Jonathan W. Yewdell, Angel Porgador*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

770 Scopus citations

Abstract

Natural killer (NK) cells destroy virus-infected and tumour cells, apparently without the need for previous antigen stimulation1. In part, target cells are recognized by their diminished expression of major histocompatibility complex (MHC) class I molecules, which normally interact with inhibitory receptors on the NK cell surface2-8. NK cells also express triggering receptors that are specific for non-MHC ligands; but the nature of the ligands recognized on target cells is undefined9-14. NKp46 is thought to be the main activating receptor for human NK cells9,15. Here we show that a soluble NKp46-immunoglobulin fusion protein binds to both the haemagglutinin of influenza virus and the haemagglutinin-neuraminidase of parainfluenza virus. In a substantial subset of NK cells, recognition by NKp46 is required to lyse cells expressing the corresponding viral glycoproteins. The binding requires the sialylation of NKp46 oligosaccharides, which is consistent with the known sialic binding capacity of the viral glycoproteins. These findings indicate how NKp46-expressing NK cells may recognize target cells infected by influenza or parainfluenza without the decreased expression of target-cell MHC class I protein.

Original languageAmerican English
Pages (from-to)1055-1060
Number of pages6
JournalNature
Volume409
Issue number6823
DOIs
StatePublished - 22 Feb 2001

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