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Analysis of Binding of Mannosides in Relation to Langerin (CD207) in Langerhans Cells of Normal and Transformed Epithelia

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Abstract

Tandem-repeat C-type lectins (pattern-recognition receptors) with specificity for mannosides are intimately involved in antigen recognition, uptake, routing and presentation in macrophages and dendritic cells. In Langerhans cells, Langerin (CD207), a type-II transmembrane protein with a single C-type carbohydrate recognition domain attached to a heptad repeat in the neck region, which is likely to establish oligomers with an α-coiled-coil stalk, has been implicated in endocytosis and the formation of Birbeck granules. The structure of Langerin harbours essential motifs for Ca2+-binding and sugar accommodation. Lectin activity has previously been inferred by diminished antibody binding to cells in the presence of the glycan ligand mannan. In view of the complexity of the C-type lectin/lectin-like network, it is unclear what role Langerin plays for Langerhans cells in binding mannosides. In order to reveal in frozen tissue sections to what extent mannose-binding activity co-localizes with Langerin, we have used a synthetic marker, i.e. a neoglycoprotein carrying mannose maxiclusters, as a histochemical ligand, and computer-assisted fluorescence monitoring in a double-labelling procedure. Mannoside-binding capacity was detected in normal epithelial cells. Double labelling ensured the unambiguous assessment of the binding of the neoglycoprotein in Langerhans cells. Light-microscopically, its localization profile resembled the pattern of immunohistochemical detection of Langerin. This result has implications for suggesting rigorous controls in histochemical analysis of this cell type, because binding of kit reagents, i.e. mannose-rich glycoproteins horseradish peroxidase or avidin, to Langerin (or a spatially closely associated lectin) could yield false-positive signals. To show that recognition of carbohydrate ligands in dendritic cells is not restricted to mannose clusters, we have also documented binding of carrier-immobilized histo-blood group A trisaccharide, a ligand of galectin-3, which was not affected by the presence of a blocking antibody to Langerin. Remarkably, access to the carbohydrate recognition domain of Langerin appeared to be impaired in proliferatively active environments (malignancies, hair follicles), indicating presence of an endogenous ligand with high affinity to saturate the C-type lectin under these conditions.

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Authors and Affiliations

  1. Institute of Anatomy, Charles University, Prague, Czech Republic

    Jan Plzák, Zuzana Holíková & Karel Smetana Jr

  2. Department of Otorhinolaryngology, Head and Neck Surgery, 1st Faculty of Medicine, Charles University, Prague, Czech Republic

    Jan Plzák & Jan Betka

  3. Center of Cell Therapy and Tissue Repair, Charles University, Prague, Czech Republic

    Zuzana Holíková

  4. Department of Dermatovenerology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic

    Zuzana Holíková & Jana Hercogová

  5. Center of Cell Therapy and Tissue Repair, Charles University, Prague, Czech Republic

    Barbora Dvořánková & Karel Smetana Jr

  6. Department of Burn Surgery, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic

    Barbora Dvořánková

  7. Schering-Plough, Laboratory for Immunological Research, Dardilly, France

    Sem Saeland

  8. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia

    Nicolai V. Bovin

  9. Ludwig-Maximilians-University Munich, Munich, Germany

    Hans-Joachim Gabius

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  1. Jan Plzák
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Plzák, J., Holíková, Z., Dvořánková, B. et al. Analysis of Binding of Mannosides in Relation to Langerin (CD207) in Langerhans Cells of Normal and Transformed Epithelia. Histochem J 34, 247–253 (2002). https://doi.org/10.1023/A:1021793530802

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