Enhanced major histocompatibility complex class I-dependent presentation of antigens modified with cationic and fusogenic peptides

Nat Biotechnol. 2000 Dec;18(12):1269-72. doi: 10.1038/82377.


Soluble extracellular protein antigens are notoriously poor stimulators of CD8+ cytotoxic T-lymphocyte (CTL) responses, largely because these antigens have inefficient access to an endogenous cytosolic pathway of the major histocompatibility complex (MHC) class I-dependent antigen presentation. Here, we present a strategy that facilitates antigen penetration into the cytosol of antigen-presenting cells (APC) by addition to the antigen of charge-modifying peptide sequences. As a result of this intervention, the charge modification enhances antigen uptake into APC by counteracting the repulsive cell surface charge, and then endosomal membranes are disrupted with a subsequent release of antigen into the cytosol. This technology significantly improves MHC class I-dependent antigen presentation to CTL, enabling a more efficient generation of specific CTL immunity in vivo. The strategy described here has potential for use in developing efficient vaccines for antigen-specific immunotherapy of human malignancies.

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigens / chemistry*
  • Antigens / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus*
  • Hemagglutinins / chemistry
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Hybridomas
  • Immunologic Memory
  • Mice
  • Mice, Inbred C57BL
  • Ovalbumin / chemistry
  • Ovalbumin / immunology
  • Peptide Fragments / chemistry
  • Peptides / chemistry*
  • T-Lymphocytes, Cytotoxic / immunology*


  • Antigens
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins
  • Histocompatibility Antigens Class I
  • Peptide Fragments
  • Peptides
  • influenza virus hemagglutinin peptide 2 (1-25)
  • Ovalbumin