Vaccination With Cytotoxic T Lymphocyte Epitope-Containing Peptide Protects Against a Tumor Induced by Human Papillomavirus Type 16-transformed Cells

Eur J Immunol. 1993 Sep;23(9):2242-9. doi: 10.1002/eji.1830230929.

Abstract

Cytotoxic T lymphocyte (CTL) peptide epitopes can be used for immunization of mice against lethal virus infection. To study whether this approach can be successful against virus-induced tumors we generated a B6 (H-2b) tumorigenic cell line transformed by human papillomavirus (HPV). This virus is detected in over 90% of all human cervical cancers. To identify vaccine candidates, we generated a set of 240 overlapping peptides derived from the HPV type 16 (HPV16) oncogenes E6 and E7. These peptides were tested for their ability to bind H-2Kb and H-2Db MHC class I molecules. Binding peptides were compared with the presently known peptide-binding motifs for H-2Kb and H-2Db and the predictive value of these motifs is shortly discussed. The high-affinity H-2Db-binding peptide and putative CTL epitope E7 49-57 (RAHYNIVTF) was used in vaccination studies against HPV 16-transformed tumor cells. Immunization with peptide E7 49-57 rendered mice insensitive to a subsequent challenge with HPV 16-transformed tumor cells in vivo, and induced a CTL response which lysed the tumor cells in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cell Line, Transformed
  • Epitopes / immunology*
  • Histocompatibility Antigens Class I / immunology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Oncogene Proteins, Viral / immunology
  • Papillomaviridae / immunology*
  • Papillomavirus E7 Proteins
  • Peptide Fragments / immunology*
  • Repressor Proteins*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Virus Infections / prevention & control*
  • Vaccination
  • Viral Vaccines / immunology*

Substances

  • E6 protein, Human papillomavirus type 16
  • Epitopes
  • Histocompatibility Antigens Class I
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Peptide Fragments
  • Repressor Proteins
  • Viral Vaccines
  • oncogene protein E7, Human papillomavirus type 16