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Cross-dressed CD8α⁺/CD103⁺ dendritic cells prime CD8⁺ T cells following vaccination

Author:
Li, Lijin, Kim, Sojung, Herndon, John M., Goedegebuure, Peter, Belt, Brian A., Satpathy, Ansuman T., Fleming, Timothy P., Hansen, Ted H., Murphy, Kenneth M., Gillanders, William E.
Source:
Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.31 pp. 12716-12721
ISSN:
0027-8424
Subject:
antigen presentation, antigens, cytotoxic T-lymphocytes, dendritic cells, immune response, neoplasms, vaccination, vaccines
Abstract:
Activation of naïve cluster of differentiation (CD)8 ⁺ cytotoxic T lymphocytes (CTLs) is a tightly regulated process, and specific dendritic cell (DC) subsets are typically required to activate naive CTLs. Potential pathways for antigen presentation leading to CD8 ⁺ T-cell priming include direct presentation, cross-presentation, and cross-dressing. To distinguish between these pathways, we designed single-chain trimer (SCT) peptide–MHC class I complexes that can be recognized as intact molecules but cannot deliver antigen to MHC through conventional antigen processing. We demonstrate that cross-dressing is a robust pathway of antigen presentation following vaccination, capable of efficiently activating both naïve and memory CD8 ⁺ T cells and requires CD8α ⁺/CD103 ⁺ DCs. Significantly, immune responses induced exclusively by cross-dressing were as strong as those induced exclusively through cross-presentation. Thus, cross-dressing is an important pathway of antigen presentation, with important implications for the study of CD8 ⁺ T-cell responses to viral infection, tumors, and vaccines.
Agid:
1721911