Characterization of murine MGL1 and MGL2 C-type lectins: distinct glycan specificities and tumor binding properties.
Antigen presenting cells (APC) express a variety of pattern recognition receptors, including the C-type lectin receptors (CLR) that specifically recognize carbohydrate structures expressed on self-tissue and pathogens. The CLR play an important role in antigen uptake and presentation and have been shown to mediate cellular interactions. The ligand specificity of the human macrophage galactose-type lectin (MGL) has been characterized extensively. Here, we set out to determine the glycan specificity of the murine homologues, MGL1 and MGL2, using a glycan array. Murine MGL1 was found to be highly specific for Lewis X and Lewis A structures, whereas mMGL2, more similar to the human MGL, recognized N-acetylgalactosamine (GalNAc) and galactose, including the O-linked Tn-antigen, TF-antigen and core 2. The generation of MGL1 and MGL2-Fc proteins allowed us to identify ligands in lymph nodes, and MGL1-Fc additionally recognized high endothelial venules. Strikingly, MGL2 interacted strongly to adenocarcinoma cells, suggesting a potential role in tumor immunity.
Singh
Satwinder Kaur
SK
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Streng-Ouwehand
Ingeborg
I
Litjens
Manja
M
Weelij
Danny R
DR
García-Vallejo
Juan Jesús
JJ
van Vliet
Sandra J
SJ
Saeland
Eirikur
E
van Kooyk
Yvette
Y
D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001212:Asialoglycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008198:Lymph Nodes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011134:Polysaccharides / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism
D001212:Asialoglycoproteins; C064720:Clec10a protein, mouse; D037181:Lectins, C-Type; D008024:Ligands; C464940:MGL2 protein, mouse; D008565:Membrane Proteins; D011134:Polysaccharides; D011994:Recombinant Proteins