Cross-dressed CD8α+/CD103+ dendritic cells prime CD8+ T cells following vaccination.
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.
Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA.
Lijin
L
Li
Sojung
S
Kim
John M
JM
Herndon
Peter
P
Goedegebuure
Brian A
BA
Belt
Ansuman T
AT
Satpathy
Timothy P
TP
Fleming
Ted H
TH
Hansen
Kenneth M
KM
Murphy
William E
WE
Gillanders
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D039001:Integrin alpha Chains / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000235:genetics / Q000276:immunology; D014611:Vaccination
D015703:Antigens, CD; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D015395:Histocompatibility Antigens Class I; D039001:Integrin alpha Chains; D010455:Peptides; C091367:alpha E integrins