Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 40, Issue 1, Pages 36-46Publisher
WILEY
DOI: 10.1002/eji.200939748
Keywords
DC; FLt3L; poly IC
Categories
Funding
- MAID [AI13013, AI40874]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R37AI013013, R01AI013013, R01AI040874] Funding Source: NIH RePORTER
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DC present exogenous proteins to MHC class I-restricted CD8(+) T cells. This function does not require endogenous antigen synthesis within DC, providing the potential to elicit CD8(+) T-cell responses to immune complexes, inactivated microbes, dying cells, and proteins such as OVA. In mice, the CD8(+) or DEC-205(+) DC are specialized for cross-presentation, and this subset can be increased 10-fold in numbers following Fms-like tyrosine kinase 3 ligand (Flt3L) treatment in vivo. Therefore, we studied cross-presentation by abundant Flt3L DC using HIV gag protein. When enriched by positive selection with anti-CD11c beads, cells from Flt3L mice are not only more abundant but are also more highly enriched in CD11c(high) DC, particularly the DEC-205(+) subset. DC cross-present HIV gag to primed CD8(+) T cells, but when the antigen is delivered within an antibody to DEC-205 receptor, cross-presentation becomes 100-fold more efficient than non-targeted antigen. This finding requires gag to be engineered into anti-DEC antibody, not just mixed with antibody. Flt3L DC are a valuable tool to study cross-presentation, since their use overcomes the obstacle posed by the low number of cross-presenting DC in the steady state. These findings support future experiments to use Flt3L to enhance presentation of DC-targeted vaccines.
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