title: 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.
authors.affiliation: Department of Immunohematology and Blood Bank, Leiden University Medical Center, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Tan
authors.forename: A M
authors.initials: AM
authors.lastname: Mommaas
authors.forename: J W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: R
authors.initials: R
authors.lastname: Jordens
authors.forename: J J
authors.initials: JJ
authors.lastname: Onderwater
authors.forename: D
authors.initials: D
authors.lastname: Verwoerd
authors.forename: A A
authors.initials: AA
authors.lastname: Mulder
authors.forename: A N
authors.initials: AN
authors.lastname: van der Heiden
authors.forename: D
authors.initials: D
authors.lastname: Scheidegger
authors.forename: L C
authors.initials: LC
authors.lastname: Oomen
authors.forename: T H
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: A
authors.initials: A
authors.lastname: Tulp
authors.forename: J J
authors.initials: JJ
authors.lastname: Neefjes
authors.forename: F
authors.initials: F
authors.lastname: Koning
mesh_terms: D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000502:physiology*; D002451:Cell Compartmentation; D003713:Dendritic Cells / Q000502:physiology*; D004705:Endocytosis; D006681:HLA-D Antigens / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007156:Immunologic Memory; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011956:Receptors, Cell Surface / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*
chemical_list: D006681:HLA-D Antigens; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D010455:Peptides; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C025363:mannoproteins