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.
Bloushtain
Noga
N
Department of Microbiology and Immunology, Faculty of Health Sciences, and the Cancer Research Center, Ben Gurion University of the Negev, Beer Sheva, Israel.
Qimron
Udi
U
Bar-Ilan
Ahuva
A
Hershkovitz
Oren
O
Gazit
Roi
R
Fima
Eyal
E
Korc
Murray
M
Vlodavsky
Israel
I
Bovin
Nicolai V
NV
Porgador
Angel
A
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