Mannose receptor‐mediated uptake of antigens strongly enhances HLA class II‐restricted antigen presentation by cultured dendritic cells

Abstract

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 clones compared to non-mannosylated peptides. Our results indicate that mannosylation of antigen leads to selective targeting and subsequent superior presentation by DC which may be applicable in vaccine design.

Distribution and Function of Macrophage Galactose-type C-type Lectin 2 (MGL2/CD301b)

“…Mannosylated-bovine serum albumin or mannosylated peptides were presented more efficiently than non-mannosylated forms by monocyte-derived DCs (44). Such efficient uptake of mannosylated antigens was likely to be mediated by MR and/or DC-SIGN.…”

A role for exposed mannosylations in presentation of human therapeutic self-proteins to CD4+ T lymphocytes

“…CD206 has been implicated in the homeostasis of several proinflammatory mannosylated serum glycoproteins (29). Conversely, CD206 has been shown to mediate the endocytosis of a number of microbial antigens by virtue of their exposed mannosylation, thus enhancing antigenspecific T cell responses (12,30). Interestingly, the interaction of the thyroid antigens with CD206 on APCs located in the gland or draining lymph nodes has been implicated in pathological autoimmune responses to thyroid antigens (31,32).…”

Effect of Differential N-linked and O-linked Mannosylation on Recognition of Fungal Antigens by Dendritic Cells

“…In comparison, MMR-mediated endocytosis selectively and efficiently captures mannosylated antigens [13]. Both mechanisms of antigen capture result in delivery to MHC class II compartments [13], [15], [16] but antigen internalized via mannose-specific CLRs are significantly more potent at augmenting in vitro T cell proliferation [1], [2], [17], [18].…”