MANNOSE RECEPTOR-MEDIATED UPTAKE OF ANTIGENS STRONGLY ENHANCES HLA CLASS II-RESTRICTED ANTIGEN PRESENTATION BY CULTURED DENDRITIC CELLS

Dendritic cells (DC) efficiently take up antigens by macropinocytosis and mannose receptor-mediated endocytosis. Here we show that endocytos is of mannose receptor-antigen complexes takes glace via small coated vesicles, while non-mannosylated antigens were mainly present in large r vesicles, Shortly after internalization the mannose receptor and its ligand appeared in the larger vesicles. Within 10 min, the mannosylat ed and non-mannosylated antigens co-localized with typical markers for major histocompatibility complex class II-enriched compartments and l ysosomes. In contrast, the mannose receptor appeared not to reach thes e compartments, suggesting that it releases its ligand in an earlier e ndosomal structure. Moreover wee demonstrate that mannosylation of pro tein antigen and peptides resulted in a 280-10000-fold enhanced potenc y to stimulate HLA class II-restricted peptide-specific T cell clones compared to non-mannosylated peptides. Our results indicate that manno sylation of antigen leads to selective targeting and subsequent superi or presentation by DC which may be applicable in vaccine design.