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

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.
Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.31 pp. 12716-12721
antigen presentation, antigens, cytotoxic T-lymphocytes, dendritic cells, immune response, neoplasms, vaccination, vaccines
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.