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Dendritic cells (DC) efficiently take up antigens by macropinocytosis and mannose receptor‐mediated endocytosis. Here we show that endocytosis of mannose receptor‐antigen complexes takes place via small coated vesicles, while non‐mannosylated antigens were mainly present in larger vesicles. Shortly after internalization the mannose receptor and its ligand appeared in the larger vesicles. Within 10 min, the mannosylated and non‐mannosylated antigens co‐localized with typical markers for major histocompatibility complex class II‐enriched compartments and lysosomes. In contrast, the mannose receptor appeared not to reach these compartments, suggesting that it releases its ligand in an earlier endosomal structure. Moreover, we demonstrate that mannosylation of protein antigen and peptides resulted in a 200–10 000‐fold enhanced potency to stimulate HLA class II‐restricted peptide‐specific T cell …