gag protein, dendritic cell, CD8+ T lymphocyte, HIV, interferon production, major histocompatibility antigen class 1
Optimal HIV vaccines should elicit CD8+ T cells specific for HIV proteins presented on MHC class I products, because these T cells contribute to host resistance to viruses. We had previously found that the targeting of antigen to dendritic cells (DCs) in mice efficiently induces CD8+ T cell responses. To extend this finding to humans, we introduced the HIV p24 gag protein into a mAb that targets DEC-205/CD205, an endocytic receptor of DCs. We then assessed cross-presentation, which is the processing of nonreplicating internalized antigen onto MHC class I for recognition by CD8+ T cells. Low doses of αDEC-gag, but not control Ig-gag, stimulated proliferation and IFN-γ production by CD8+ T cells isolated from the blood of HIV-infected donors. αCD205 fusion mAb was more effective for cross-presentation than αD209/DC-SIGN, another abundant DC uptake receptor. Presentation was diverse, because we identified eight different gag peptides that were recognized via DEC-205 in 11 individuals studied consecutively. Our results, based on humans with highly polymorphic MHC products, reveal that DCs and DEC-205 can cross-present several different peptides from a single protein. Because of the consistency in eliciting CD8 + T cell responses, these data support the testing of αDEC-205 fusion mAb as a protein-based vaccine.
Bozzacco, L., C. Trumpfheller, F. P. Siegal, S. Mehandru, M. Markowitz, M. Carrington, M. C. Nussenzweig, A. G. Piperno, and R. M. Steinman. 2007. "DEC-205 Receptor on Dendritic Cells Mediates Presentation of HIV Gag Protein to CD8+ T Cells in a Spectrum of Human MHC I Haplotypes." Proceedings of the National Academy of Sciences of the United States of America 104 (4): 1289-1294