Membrane-associated heparan sulfate proteoglycans are involved in the recognition of cellular targets by NKp30 and NKp46.
Lysis of virus-infected and tumor cells by NK cells is mediated via natural cytotoxicity receptors (NCRs). We have recently shown that the NKp44 and NKp46 NCRs, but not the NKp30, recognize viral hemagglutinins. In this study we explored the nature of the cellular ligands recognized by the NKp30 and NKp46 NCRs. We demonstrate that target cell surface heparan sulfate proteoglycans (HSPGs) are recognized by NKp30 and NKp46 and that 6-O-sulfation and N-acetylation state of the glucose building unit affect this recognition and lysis by NK cells. Tumor cells expressing cell surface heparanase, CHO cells lacking membranal heparan sulfate and glypican-1-suppressed pancreatic cancer cells manifest reduced recognition by NKp30 and NKp46 and are lysed to a lesser extent by NK cells. Our results are the first clue for the identity of the ligands for NKp30 and NKp46. Whether the ligands are particular HSPGs, unusual heparan sulfate epitopes, or a complex of HSPGs and either other protein or lipid moieties remains to be further explored.
Department of Microbiology and Immunology, Faculty of Health Sciences, and the Cancer Research Center, Ben Gurion University of the Negev, Beer Sheva, Israel.
Noga
N
Bloushtain
Udi
U
Qimron
Ahuva
A
Bar-Ilan
Oren
O
Hershkovitz
Roi
R
Gazit
Eyal
E
Fima
Murray
M
Korc
Israel
I
Vlodavsky
Nicolai V
NV
Bovin
Angel
A
Porgador
D000818:Animals; D002241:Carbohydrates / Q000276:immunology*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D019812:Heparan Sulfate Proteoglycans / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D011971:Receptors, Immunologic
D002241:Carbohydrates; D019812:Heparan Sulfate Proteoglycans; D008565:Membrane Proteins; D011971:Receptors, Immunologic