Geographic and functional coupling of CD1 isoforms and C-type lectins. (A) CD1a molecules are transported from the cell surface to early recycling vesicles and Birbeck granules. Glycolipid antigens captured by langerin are also internalized selectively to Birbeck granules, where CD1a is coupled with lipid moieties. This pathway enables LCs to present lipid antigens to CD1a-restricted T cells. (B) CD1b molecules recycle to early endosomes and then late endosomes, and MMR and DC-SIGN deliver glycolipid antigens to these subcompartments, respectively. Certain DC subsets (e.g., dermal DCs) may employ these pathways for CD1b-restricted lipid antigen presentation. (C) Glycoprotein antigens can be internalized via DEC-205 to MIICs, where peptide antigens bind to MHC class II molecules. This pathway presumably promotes MHC II–restricted peptide antigen presentation by many DC subsets known to express DEC-205.