The Dominant Role of CD8⁺ Dendritic Cells in Cross-Presentation Is Not Dictated by Antigen Capture

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 28; pp. 10729 - 10734
• Main Authors: Schnorrer, Petra, Behrens, Georg M. N., Wilson, Nicholas S., Pooley, Joanne L., Smith, Christopher M., El-Sukkari, Dima, Davey, Gayle, Kupresanin, Fiona, Li, Ming, Maraskovsky, Eugene, Belz, Gabrielle T., Carbone, Francis R., Shortman, Ken, Heath, William R., Villadangos, Jose A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 11.07.2006; National Acad Sciences
• Subjects: Animals; Antigens; Antigens - metabolism; Antigens, Bacterial - immunology; Antigens, Bacterial - metabolism; Biological Sciences; CD8 Antigens - biosynthesis; Cells, Cultured; Cross priming; Cross-Priming - immunology; Cytometry; Dendritic Cells - immunology; Dendritic Cells - metabolism; Latex; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Mice, Transgenic; Microspheres; Molecules; Ova; Ovalbumin - immunology; Ovalbumin - metabolism; Spleen; Spleen - cytology; Spleen - immunology; Spleen - metabolism; Spleen cells; Splenocytes; T lymphocytes; Vaccination
• DOI: 10.1073/pnas.0601956103
• ISSN: 0027-8424

Mouse spleens contain three populations of conventional ($CD11c^{high}$) dendritic cells (DCs) that play distinct functions. The CD8⁺ DC are unique in that they can present exogenous antigens on their MHC class I molecules, a process known as cross-presentation. It is unclear whether this special ability is because only the CD8⁺ DC can capture the antigens used in cross-presentation assays, or because this is the only DC population that possesses specialized machinery for cross-presentation. To solve this important question we examined the splenic DC subsets for their ability to both present via MHC class II molecules and cross-present via MHC class I using four different forms of the model antigen ovalbumin (OVA). These forms include a cell-associated form, a soluble form, OVA expressed in bacteria, or OVA bound to latex beads. With the exception of bacterial antigen, which was poorly cross-presented by all DC, all antigenic forms were cross-presented much more efficiently by the CD8⁺ DC. This pattern could not be attributed simply to a difference in antigen capture because all DC subsets presented the antigen via MHC class II. Indeed, direct assessments of endocytosis showed that CD8⁺ and CD8⁻ DC captured comparable amounts of soluble and bead-associated antigen, yet only the CD8⁺ DC cross-presented these antigenic forms. Our results indicate that cross-presentation requires specialized machinery that is expressed by CD8⁺ DC but largely absent from CD8⁻ DC. This conclusion has important implications for the design of vaccination strategies based on antigen targeting to DC.