Efficient cross-presentation of soluble exogenous antigens introduced into dendritic cells using a weak-based amphiphilic peptide.
To develop a novel dendritic cell (DC)-based vaccine for inducing antigen-specific CD8+ T cell responses by cross-presentation, we tested a novel antigen delivery system that introduces soluble antigens into the cytosol of cells by an endocytosis-mediated mechanism which avoids damaging the plasma membrane ("Endo-Porter"). Proteins released from endosomes into the cytoplasm are degraded by the proteasome, and fragmented antigenic peptides are presented to the classical cytosolic MHC class I pathway. DCs pulsed with OVA protein in the presence of Endo-Porter efficiently stimulate OVA peptide-specific CD8+ T (OT-I) cells. Although this agent diverts some of the endocytosed antigens away from the classical MHC class II-restricted presentation pathway to the class I pathway, the activation of CD4+ T cells was found not to be hampered by Endo-Porter-mediated antigen delivery. On the contrary, it was rather augmented, probably due to the increased uptake of antigen. Because specific CD4+ T cell help is required to license DCs for cross-priming, Endo-Porter-mediated antigen delivery is a promising approach for developing more efficient cancer vaccines targeting both CD4+ and CD8+ T cells.
Ikeuchi
Nobuhito
N
Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan.
Futami
Junichiro
J
Hosoi
Akihiro
A
Noji
Shuichi
S
Kurachi
Makoto
M
Ueha
Satoshi
S
Fujii
Shin-Ichiro
S
Yamada
Hidenori
H
Matsushima
Koji
K
Moriyasu
Fuminori
F
Kakimi
Kazuhiro
K
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045142:Cross-Priming; D003600:Cytosol / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000378:metabolism*
D000941:Antigens; D019496:Cancer Vaccines; C511217:Endo-Porter; D015395:Histocompatibility Antigens Class I; D010455:Peptides