title: Antigen delivery to early endosomes eliminates the superiority of human blood BDCA3+ dendritic cells at cross presentation.
abstract: Human BDCA3(+) dendritic cells (DCs), the proposed equivalent to mouse CD8α(+) DCs, are widely thought to cross present antigens on MHC class I (MHCI) molecules more efficiently than other DC populations. If true, it is unclear whether this reflects specialization for cross presentation or a generally enhanced ability to present antigens on MHCI. We compared presentation by BDCA3(+) DCs with BDCA1(+) DCs using a quantitative approach whereby antigens were targeted to distinct intracellular compartments by receptor-mediated internalization. As expected, BDCA3(+) DCs were superior at cross presentation of antigens delivered to late endosomes and lysosomes by uptake of anti-DEC205 antibody conjugated to antigen. This difference may reflect a greater efficiency of antigen escape from BDCA3(+) DC lysosomes. In contrast, if antigens were delivered to early endosomes through CD40 or CD11c, BDCA1(+) DCs were as efficient at cross presentation as BDCA3(+) DCs. Because BDCA3(+) DCs and BDCA1(+) DCs were also equivalent at presenting peptides and endogenously synthesized antigens, BDCA3(+) DCs are not likely to possess mechanisms for cross presentation that are specific to this subset. Thus, multiple DC populations may be comparably effective at presenting exogenous antigens to CD8(+) T cells as long as the antigen is delivered to early endocytic compartments.
authors.affiliation: Genentech, South San Francisco, CA 94080, USA.
authors.forename: Lillian
authors.initials: L
authors.lastname: Cohn
authors.forename: Bithi
authors.initials: B
authors.lastname: Chatterjee
authors.forename: Filipp
authors.initials: F
authors.lastname: Esselborn
authors.forename: Anna
authors.initials: A
authors.lastname: Smed-Sörensen
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nakamura
authors.forename: Cécile
authors.initials: C
authors.lastname: Chalouni
authors.forename: Byoung-Chul
authors.initials: BC
authors.lastname: Lee
authors.forename: Richard
authors.initials: R
authors.lastname: Vandlen
authors.forename: Tibor
authors.initials: T
authors.lastname: Keler
authors.forename: Peter
authors.initials: P
authors.lastname: Lauer
authors.forename: Dirk
authors.initials: D
authors.lastname: Brockstedt
authors.forename: Ira
authors.initials: I
authors.lastname: Mellman
authors.forename: Lélia
authors.initials: L
authors.lastname: Delamarre
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D018949:Antigens, CD1; D000954:Antigens, Surface / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism; D002451:Cell Compartmentation; D002469:Cell Separation; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D011992:Endosomes / Q000276:immunology*; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D008247:Lysosomes / Q000276:immunology; D051379:Mice; D015778:Minor Histocompatibility Antigens; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D018180:Thrombomodulin
chemical_list: D000941:Antigens; D015703:Antigens, CD; D018949:Antigens, CD1; D000954:Antigens, Surface; C437944:CD1C protein, human; D019013:CD40 Antigens; C093569:DEC-205 receptor; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; C546931:THBD protein, human; D018180:Thrombomodulin