Cytotoxic T lymphocytes raised against a subdominant epitope offered as a synthetic peptide eradicate human papillomavirus type 16-induced tumors

Eur J Immunol. 1995 Sep;25(9):2638-42. doi: 10.1002/eji.1830250935.


Previously, we have shown that immunization with human papillomavirus (HPV) type 16-derived cytotoxic T lymphocyte (CTL) epitope E7 49-57 (RAHYNIVTF) renders C57BL/6 mice insensitive to tumors formed by HPV16-transformed cells. In this study, we provide evidence that E7 49-57 is expressed as a subdominant CTL epitope on HPV16-transformed C57BL/6 cells. Using acid peptide elution, it is shown that HPV16-transformed cells express another CTL epitope, besides E7 49-57, which appears to be dominant. We demonstrate that a CTL line raised against the subdominant CTL epitope, offered as synthetic peptide E7 49-57, eradicates established HPV16-induced tumors in mice. Our data show that synthetic peptide-induced CTL can be applied successfully in vivo against (virus-induced) tumor, and emphasize that subdominant CTL epitopes are useful targets for immunotherapy. Furthermore, it is illustrated for the first time that HPV16-specific CTL interfere directly with HPV16-induced tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Line, Transformed
  • Cell Transformation, Viral
  • Epitopes / immunology
  • Humans
  • Immunotherapy, Adoptive*
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / immunology*
  • Papillomaviridae / chemistry
  • Papillomaviridae / immunology*
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / immunology
  • Tumor Virus Infections / immunology*


  • Epitopes
  • Peptides