Antigen delivery to early endosomes eliminates the superiority of human blood BDCA3+ dendritic cells at cross presentation

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. ©2013 Cohn et al.