Efficient cross-presentation of soluble exogenous antigens introduced into dendritic cells using a weak-based amphiphilic peptide

Nobuhito Ikeuchi, Junichiro Futami, Akihiro Hosoi, Shuichi Noji, Makoto Kurachi, Satoshi Ueha, Shin ichiro Fujii, Hidenori Yamada, Koji Matsushima, Fuminori Moriyasu, Kazuhiro Kakimi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)217-222
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume392
Issue number2
DOIs
Publication statusPublished - Feb 5 2010

Keywords

  • Cross-presentation
  • DC vaccine
  • Dendritic cell
  • Endo-Porter

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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