TY - JOUR
T1 - Cross-dressed CD8α+/CD103+ dendritic cells prime CD8+ T cells following vaccination
AU - Li, Jin
AU - Kim, Sojung
AU - Herndon, John M.
AU - Goedegebuure, Peter
AU - Belt, Brian A.
AU - Satpathy, Ansuman T.
AU - Fleming, Timothy P.
AU - Hansen, Ted H.
AU - Murphy, Kenneth M.
AU - Gillanders, William E.
PY - 2012/7/31
Y1 - 2012/7/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84864517178&partnerID=8YFLogxK
U2 - 10.1073/pnas.1203468109
DO - 10.1073/pnas.1203468109
M3 - Article
C2 - 22802630
AN - SCOPUS:84864517178
SN - 0027-8424
VL - 109
SP - 12716
EP - 12721
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 31
ER -