Identification and characterization of an alternatively spliced isoform of mouse Langerin/CD207

Abstract

The mouse homologue of human Langerin (CD207), a novel Langerhans cells (LC)-restricted C-type lectin that likely participates in antigen recognition and uptake, has been recently identified. In this study, we isolated the mouse Langerin cDNA from murine fetal skin-derived dendritic cells (FSDDC) by subtractive cloning and rapid amplification of cDNA ends (RACE). An alternatively spliced variant of mouse Langerin that lacked the extracellular neck domain (ΔE3Langerin) was detected in RNA derived from FSDDC and epidermal LC by RT-PCR. In vitro-generated FSDDC and epidermal LC expressed both full-length and ΔE3Langerin mRNA, but tissue expression was not restricted to skin. Mouse Langerin protein isoforms were readily detected in fibroblasts transfected with cDNAs encoding epitope-tagged Langerin and ΔE3Langerin. Recombinant ΔE3Langerin protein localized with transferrin-containing compartments in transfected fibroblasts. Full-length mouse Langerin-bound mannan, whereas ΔE3Langerin and soluble bacterial recombinant Langerin protein lacking the neck domain did not. Fibroblasts transfected with mouse Langerin cDNA contained typical Birbeck granules (BG) and cored tubules, whereas ΔE3Langerin cDNA did not induce BG or cored tubule formation in transfected fibroblasts. Developmentally regulated expression of Langerin isoforms provides a mechanism by which Langerin involvement in antigen uptake and processing could be regulated.