Characterization of murine MGL1 and MGL2 C-type lectins: distinct glycan specificities and tumor binding properties

Mol Immunol. 2009 Mar;46(6):1240-9. doi: 10.1016/j.molimm.2008.11.021. Epub 2009 Jan 21.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / metabolism
  • Animals
  • Antigen-Presenting Cells / immunology
  • Asialoglycoproteins / genetics
  • Asialoglycoproteins / immunology
  • Asialoglycoproteins / metabolism*
  • Bone Marrow Cells / metabolism
  • Cell Line, Tumor
  • Cells, Cultured
  • Endothelium, Vascular / metabolism
  • Extracellular Matrix / metabolism
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology
  • Lectins, C-Type / metabolism*
  • Ligands
  • Lymph Nodes / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Polysaccharides / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Skin / metabolism

Substances

  • Asialoglycoproteins
  • Clec10a protein, mouse
  • Lectins, C-Type
  • Ligands
  • MGL2 protein, mouse
  • Membrane Proteins
  • Polysaccharides
  • Recombinant Proteins