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

J Exp Med. 2013 May 6;210(5):1049-63. doi: 10.1084/jem.20121251. Epub 2013 Apr 8.

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.

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • Antigens / immunology*
  • Antigens, CD / metabolism
  • Antigens, CD1
  • Antigens, Surface / metabolism*
  • CD40 Antigens / metabolism
  • Cell Compartmentation
  • Cell Separation
  • Cross-Priming / immunology*
  • Dendritic Cells / immunology*
  • Endosomes / immunology*
  • Glycoproteins
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Lectins, C-Type / metabolism
  • Lysosomes / immunology
  • Mice
  • Minor Histocompatibility Antigens
  • Phenotype
  • Receptors, Cell Surface / metabolism

Substances

  • Antigens
  • Antigens, CD
  • Antigens, CD1
  • Antigens, Surface
  • CD1C protein, human
  • CD40 Antigens
  • DEC-205 receptor
  • Glycoproteins
  • Histocompatibility Antigens Class I
  • Lectins, C-Type
  • Minor Histocompatibility Antigens
  • Receptors, Cell Surface
  • blood dendritic cell antigen 3, human