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Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10729-34. Epub 2006 Jun 28.

The dominant role of CD8+ dendritic cells in cross-presentation is not dictated by antigen capture.

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  • 1Immunology Division and Cooperative Research Centre for Vaccine Technology, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.

Abstract

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.

PMID:
16807294
PMCID:
PMC1502299
DOI:
10.1073/pnas.0601956103
[PubMed - indexed for MEDLINE]
Free PMC Article
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