| Autor: |
Bozzacco L; Laboratory of Cellular Physiology and Immunology and Chris Browne Center, The Rockefeller University, New York, NY 10065-6399, USA., Trumpfheller C, Huang Y, Longhi MP, Shimeliovich I, Schauer JD, Park CG, Steinman RM |
| Jazyk: |
angličtina |
| Zdroj: |
European journal of immunology [Eur J Immunol] 2010 Jan; Vol. 40 (1), pp. 36-46. |
| DOI: |
10.1002/eji.200939748 |
| Abstrakt: |
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 CD11chigh 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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
Plný text