Glycobiology Advance Access originally published online on July 9, 2007
Glycobiology 2007 17(10):1104-1119; doi:10.1093/glycob/cwm073
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The C-type lectin L-SIGN differentially recognizes glycan antigens on egg glycosphingolipids and soluble egg glycoproteins from Schistosoma mansoni
2 Institute of Biochemistry, Medical Faculty, Justus-Liebig-University Giessen, Friedrichstrasse 24, D-35392 Giessen, Germany
3 Department of Molecular Cell Biology and Immunology, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
4 Centre de Recherches sur les Macromolecules Végétales, CNRS (affiliated with Université Joseph Fourier), 38041 Grenoble, Cedex 09, France
1 To whom correspondence should be addressed: Tel: +31-2-04-44-81-57; Fax: +31-2-04-44-81-44; e-mail: im.vandie{at}vumc.nl
Received on May 15, 2007; revised on June 29, 2007; accepted on June 30, 2007
Recognition of pathogen-derived carbohydrate constituents by antigen presenting cells is an important step in the induction of protective immunity. Here we investigated the interaction of L-SIGN (liver/lymph node specific ICAM-3-grabbing nonintegrin), a C-type lectin that functions as antigen receptor on human liver sinusoidal endothelial cells, with egg-derived glycan antigens of the parasitic trematode Schistosoma mansoni. Our data demonstrate that L-SIGN binds both schistosomal soluble egg antigens (SEA) and egg glycosphingolipids, and can mediate internalization of SEA by L-SIGN expressing cells. Binding and internalization of SEA was strongly reduced after treatment of SEA with endoglycosidase H, whereas defucosylation affected neither binding nor internalization. These data indicate that L-SIGN predominantly interacts with oligomannosidic N-glycans of SEA. In contrast, binding to egg glycosphingolipids was completely abolished after defucosylation. Our data show that L-SIGN binds to a glycosphingolipid fraction containing fucosylated species with compositions of Hex1HexNAc5–7dHex3–6Cer, as evidenced by mass spectrometry. The L-SIGN "gain of function" mutant Ser363Val, which binds fucosylated Lewis antigens, did not bind to this fucosylated egg glycosphingolipid fraction, suggesting that L-SIGN displays different modes in binding fucoses of egg glycosphingolipids and Lewis antigens, respectively. Molecular modeling studies indicate that the preferred binding mode of L-SIGN to the respective fucosylated egg glycosphingolipid oligosaccharides involves a Fuc
1-3GalNAcß1-4(Fuc1-3)GlcNAc tetrasaccharide at the nonreducing end. In conclusion, our data indicate that L-SIGN recognizes both oligomannosidic N-glycans and multiply fucosylated carbohydrate motifs within Schistosoma egg antigens, which demonstrates that L-SIGN has a broad but specific glycan recognition profile.
Key words: C-typelectin / glycosphingolipids / L-SIGN / parasitic helminth glycans / Schistosoma mansoni
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