Glycobiology Advance Access published online on July 9, 2007
Glycobiology, 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
,1
Institute of Biochemistry, Medical Faculty, Justus-Liebig-University Giessen, Friedrichstrasse 24, D-35392 Giessen, Germany
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
¶ Centre de Recherches sur les Macromolecules Végétales, CNRS (affiliated with Université Joseph Fourier), 38041 Grenoble, cedex 09, France
1 Address correspondence to: Dr. Irma van Die, Department of Molecular Cell Biology and Immunology, VU University Medical Center, Postbus 7057, 1007 MB Amsterdam, The Netherlands; Phone: +3120 4448157; Fax: +3120 4448144; E-mail: im.vandie{at}vumc.nl
Received on May 15, 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 non-reducing 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-type lectin / L-SIGN / glycosphingolipids / parasitic helminth glycans / Schistosoma mansoni
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