Anti-Langerin monoclonal antibody targeted to Langerin was efficiently endocytozed by Langerhans cells in vitro [121] and in vivo [122], suggesting further studies in immunizations through the skin for DC-based vaccination therapies. Indeed, anti-Langerin monoclonal antibody conjugated to HIV gag-p24 induced Th1 and CD8+ T-cell responses in mice [123]. Interestingly, Inhibitors,research,lifescience,medical anti-DEC-205 monoclonal antibody
was recently shown to be taken up by Langerin-positive DCs [124], suggesting there is cross-talk between DEC-205 and Langerin receptors. Further, a noncovalent fusion between anti-Langerin monoclonal antibody and HA1 influenza hemagglutinin elicited antigen-specific T-cell and antibody responses in vitro and in vivo [125]. 2.2.3. MGL MGL (human macrophage galactose- and N-acetylgalactosamine-specific C-type lectin) is the classical asialoglycoprotein receptor Inhibitors,research,lifescience,medical (Figure 1). MGL is highly expressed on macrophages and immature DCs, whose ligand specificity differs from DC-SIGN and L-SIGN, in that it binds to galactose and N-acetylgalactosamine leading to Th2 skewed immunity [126, 127]. In addition, MGL binds the strongest to serine, threonine O-linked glycosylated Tn antigen, a well-known human carcinoma-associated epitope, and not to sialylated Tn antigen [128, 129]. Moreover, Inhibitors,research,lifescience,medical hMGL binds to the group
of filoviruses and to gonorrhea (via lipooligosaccharides) leading to altered DC cytokine secretion profiles and stimulation of CD4+ Inhibitors,research,lifescience,medical Th responses (Table 1) [77,
126, 127]. MUC1 peptide (3 tandem repeats, 60 amino acids enzymatically glycosylated with GalNAc) or short MUC1 or MUC2 peptides containing Tn bound to immature DCs and the MUC1-Tn glycopeptide localized within the MHC class I and class II compartments [130]. MUC1 glycopeptides linked to anti-MGL antibody led to upregulation of human DC cell surface molecules and enhanced CD8+ T stimulation in vitro [131]. In mice, MGL+ CD103- dermal DCs bound to glycosylated Inhibitors,research,lifescience,medical Tn antigen in vivo, stimulating MHC class II CD4+ T-cell responses. Intradermal BI 6727 in vivo immunization with Tn-glycopeptides generates antibodies and Th2 cytokine secretion by CD4+ T cells [132]. Recently, a mimic of galactose/N-acetylgalactosamine stimulated blood monocytes and myeloid derived DCs [133], suggesting that glycosylated mimetics could be used to target antigens to MGL expressing DCs. below These results demonstrate that the targeting of MGL receptor expressed on murine and human DCs stimulates T-cell and antibody responses, and this approach could be used to design novel anticancer vaccines. 2.2.4. Dectin-1 Subfamily Dectin-1 (dendritic cell-associated C-type lectin-1, DCAL-1, Clec7A) or beta-glucan receptor is a C-type lectin receptor which is part of the NK gene complex in the Dectin-1 cluster (Table 1 and Figure 1) [134].