Occasional memory cytotoxic T-cell responses of patients with human papillomavirus type 16-positive cervical lesions against a human leukocyte antigen-A *0201-restricted E7-encoded epitope

Cancer Res. 1996 Feb 1;56(3):582-8.

Abstract

Most cervical carcinoma (Cxca) cells constitutively express human papillomavirus type 16 (HPV16) E6 and E7 oncoproteins. These proteins are, therefore, attractive targets for T cell-based immunotherapy. Previously, we identified HVP16 E7-encoded CTL epitopes. In patients with cervical intraepithelial neoplasia or Cxca, little is known concerning T-cell activity against viruses in general and against HPV16 in particular. Here, we have screened the blood of 10 healthy donor controls and of 22 patients with HPV16+ cervical lesions for the presence of CTLs directed against HPV16 E7- and control influenza virus matrix-derived epitopes presented by HLA-A *0201. We detected influenza virus-specific CTLs in all donors and in the majority of patients, indicating that most patients have functioning T-cell responses despite their lesions or therapeutic interventions. Moreover, we show that patients with HPV16+ lesions occasionally have memory CTLs against a HPV16 E7-encoded epitope (sequence YMLD-LQPETT), providing evidence for natural CTL immunity against HPV16 in patients with cervical lesions. Combined, these findings raise possibilities for vaccination with HPV16 E7-encoded peptides to induce or augment CTL responses for treatment or prevention of Cxca.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Epitopes / immunology*
  • Female
  • HLA-A Antigens / immunology*
  • Humans
  • Immunologic Memory / immunology*
  • Influenza A virus / immunology
  • Molecular Sequence Data
  • Oncogene Proteins, Viral / immunology*
  • Papillomaviridae / immunology*
  • Papillomavirus E7 Proteins
  • T-Lymphocytes, Cytotoxic / immunology*
  • Uterine Cervical Dysplasia / immunology
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / virology*

Substances

  • Epitopes
  • HLA-A Antigens
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • oncogene protein E7, Human papillomavirus type 16