HER-2/neu mediated down-regulation of MHC class I antigen processing prevents CTL-mediated tumor recognition upon DNA vaccination in HLA-A2 transgenic mice

Cancer Immunol Immunother. 2009 May;58(5):653-64. doi: 10.1007/s00262-008-0587-1. Epub 2008 Sep 27.


To study DNA vaccination directed against human HER-2 in the HHD mouse Tg strain, we created a novel HER-2-expressing syngeneic tumor transplantation model. We found that a DNA vaccine encoding the full length HER-2 DNA protected HHD mice from HER-2(+) tumor challenge by a CTL independent mechanism. A more efficient approach to induce HLA-A2 restricted CTLs, through immunization with a multi-epitope DNA vaccine expressing the HLA-A2 restricted HER-2 369-377, 435-443 and 689-697 epitopes, resulted in high numbers of peptide specific T cells but failed to induce tumor protection. Subsequently we discovered that HER-2 transfected tumor cells down-regulated MHC class I antigen expression and exhibited a series of defects in the antigen processing pathway which impaired the capacity to produce and display MHC class I peptide-ligands to specific CTLs. Our data demonstrate that HER-2 transfection is associated with defects in the MHC class I presentation pathway, which may be the underlying mechanism behind the inability of CTLs to recognize tumors in this HLA-A2 transgenic model. As defective MHC class I presentation may be a common characteristic of HER-2 expressing tumors, vaccines targeting HER-2 should aim at inducing an integrated immune response where also CD4(+) T cells and antibodies are important components.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation
  • Base Sequence
  • Cancer Vaccines / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • Genes, MHC Class I
  • Genes, erbB-2
  • HLA-A2 Antigen / genetics*
  • HLA-A2 Antigen / immunology
  • Humans
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Molecular Sequence Data
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / immunology*
  • Sarcoma, Experimental / chemically induced
  • Sarcoma, Experimental / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection
  • Vaccines, DNA / immunology*


  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • HLA-A2 Antigen
  • Peptide Fragments
  • Vaccines, DNA
  • ERBB2 protein, human
  • Receptor, ErbB-2