Characterization of carbohydrate recognition by langerin, a C-type lectin of Langerhans cells

Abstract

Langerin is a type II transmembrane cell surface receptor found on Langerhans cells. The extracellular domain of langerin consists of a neck region containing a series of heptad repeats and a C-terminal C-type carbohydrate-recognition domain (CRD). A role for langerin in processing of glycoprotein antigens has been proposed, but until now there has been little study of the langerin protein. In this study, analytical ultracentrifugation and circular dichroism spectroscopy of recombinant soluble fragments of human langerin have been used to show that the extracellular region of this receptor exists as a stable trimer held together by a coiled coil of alpha-helices formed by the neck region. The langerin CRD shows specificity for mannose, GlcNAc, and fucose, but only the trimeric extracellular domain fragment binds to glycoprotein ligands. Langerin extracellular domain binds mammalian high mannose oligosaccharides, as well mannose-containing structures on yeast invertase but does not bind complex glycan structures. Full-length langerin stably expressed in rat fibroblast transfectants mediates efficient uptake and degradation of a mannosylated neoglycoprotein ligand. pH-dependent ligand release appears to involve interactions between the CRDs or between the CRDs and the neck region in the trimer. The results are consistent with a role for langerin in internalization of both self and nonself glycoprotein antigens.