Characterization of the recognition of tumor cells by the natural cytotoxicity receptor, NKp44

Oren Hershkovitz, Sergey Jivov, Noga Bloushtain, Alon Zilka, Guy Landau, Ahuva Bar-Ilan, Rachel G. Lichtenstein, Kerry S. Campbell, Toin H. Van Kuppevelt, Angel Porgador

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

NKp44 is a natural cytotoxicity receptor expressed by human NK cells upon activation. In this study, we demonstrate that cell surface heparan sulfate proteoglycans (HSPGs), expressed by target cells, are involved in the recognition of tumor cells by NKp44. NKp44 showed heparan sulfate-dependent binding to tumor cells; this binding was partially blocked with an antibody to heparan sulfate. In addition, direct binding of NKp44 to heparin was observed, and soluble heparin/heparan sulfate enhanced the secretion of IFNγ by NK92 cells activated with anti-NKp44 monoclonal antibody. Basic amino acids, predicted to constitute the putative heparin/heparan sulfate binding site of NKp44, were mutated. Tumor cell recognition of the mutated NKp44 proteins was significantly reduced and correlated with their lower recognition of heparin. We previously reported that NKp44 recognizes the hemagglutinin of influenza virus (IV). Nevertheless, the ability of the mutated NKp44 proteins to bind viral hemagglutinin expressed by IV-infected cells was not affected. Thus, we suggest that heparan sulfate epitope(s) are ligands/coligands of NKp44 and are involved in its tumor recognition ability.

Original languageEnglish
Pages (from-to)7426-7436
Number of pages11
JournalBiochemistry
Volume46
Issue number25
DOIs
StatePublished - 26 Jun 2007

ASJC Scopus subject areas

  • Biochemistry

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