CD8+ T cell cross-priming via transfer of proteasome substrates

Science. 2004 May 28;304(5675):1318-21. doi: 10.1126/science.1096378.

Abstract

"Cross-priming" describes the activation of naïve CD8+ T cells by professional antigen-presenting cells that have acquired viral or tumor antigens from "donor" cells. Antigen transfer is believed to be mediated by donor cell-derived molecular chaperones bearing short peptide ligands generated by proteasome degradation of protein antigens. We show here that cross-priming is based on the transfer of proteasome substrates rather than peptides. These findings are potentially important for the rational design of vaccines that elicit CD8+ T cell responses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcysteine / analogs & derivatives*
  • Acetylcysteine / pharmacology
  • Animals
  • Antigen Presentation*
  • Antigens / immunology*
  • Antigens / metabolism
  • Antigens, Viral / immunology
  • Antigens, Viral / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Cross-Priming*
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Endoplasmic Reticulum / metabolism
  • Humans
  • Immunization
  • Influenza A virus / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Chaperones / metabolism
  • Multienzyme Complexes / metabolism*
  • Ovalbumin / immunology
  • Ovalbumin / metabolism
  • Peptide Fragments / immunology
  • Proteasome Endopeptidase Complex
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • Vaccines / immunology
  • Vaccinia virus / genetics
  • Vaccinia virus / physiology

Substances

  • Antigens
  • Antigens, Viral
  • Cysteine Proteinase Inhibitors
  • Molecular Chaperones
  • Multienzyme Complexes
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Vaccines
  • lactacystin
  • Ovalbumin
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Acetylcysteine