title: DEC-205 mediates antigen uptake and presentation by both resting and activated human plasmacytoid dendritic cells.
abstract: DEC-205 is a type I C-type lectin receptor (CLR) that is expressed on various APC subsets and has been suggested to bind necrotic and apoptotic cells. Here we study DEC-205 characteristics in plasmacytoid DCs (pDCs) obtained from healthy individuals and assess its ability to mediate antigen presentation by isolating sufficient numbers of pDCs from apheresis material obtained from stage III/IV melanoma patients. The results demonstrate that DEC-205 is expressed on human pDCs. Internalization of DEC-205 after antibody ligation is clathrin- and dynamin-dependent as it is blocked by hypertonic shock or by inhibition of dynamin activity. Antibody targeting to DEC-205 does not affect TLR-induced expression levels of co-stimulatory and MHC molecules, but clearly impairs TLR-induced IFN-α secretion by 40%. We observed that TLR-mediated signaling increases DEC-205 expression levels without affecting receptor internalization. Moreover, human pDCs retained the capacity to present antigens via DEC-205 following TLR activation.
authors.affiliation: Department of Tumor Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Jurjen
authors.initials: J
authors.lastname: Tel
authors.forename: Daniel
authors.initials: D
authors.lastname: Benitez-Ribas
authors.forename: Sander
authors.initials: S
authors.lastname: Hoosemans
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cambi
authors.forename: Gosse J
authors.initials: GJ
authors.lastname: Adema
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Tacken
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: de Vries
mesh_terms: D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology*; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D015703:Antigens, CD; C093569:DEC-205 receptor; D016898:Interferon-alpha; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors