TY - JOUR
T1 - The mechanisms controlling the recognition of tumor- and virus-infected cells by NKp46
AU - Arnon, Tal I.
AU - Achdout, Hagit
AU - Lieberman, Niva
AU - Gazit, Roi
AU - Gonen-Gross, Tsufit
AU - Katz, Gil
AU - Bar-Ilan, Ahuva
AU - Bloushtain, Noga
AU - Lev, Marianna
AU - Joseph, Aviva
AU - Kedar, Eli
AU - Porgador, Angel
AU - Mandelboim, Ofer
PY - 2004/1/15
Y1 - 2004/1/15
N2 - 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 hemgglutinin-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 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.
AB - 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 hemgglutinin-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 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.
UR - http://www.scopus.com/inward/record.url?scp=9144250952&partnerID=8YFLogxK
U2 - 10.1182/blood-2003-05-1716
DO - 10.1182/blood-2003-05-1716
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C2 - 14504081
AN - SCOPUS:9144250952
SN - 0006-4971
VL - 103
SP - 664
EP - 672
JO - Blood
JF - Blood
IS - 2
ER -