HLA-A2-restricted peripheral blood cytolytic T lymphocyte response to HPV type 16 proteins E6 and E7 from patients with neoplastic cervical lesions

Cancer Immunol Immunother. 1996 Mar;42(3):151-60. doi: 10.1007/s002620050265.


The DNA from human papillomavirus (HPV) can be detected in 90% of cervical carcinomas. To address whether patients infected with HPV can mount efficient T cell responses to this pathogen we examined the cytotoxic T lymphocyte (CTL) response of peripheral blood mononuclear cells (PBMC) from patients with abnormal genital epithelial cells. PBMC from 11 HLA-A2+ patients were stimulated with CaSki, a cervical carcinoma cell line that is HPV 16+ and HLA-A2+. The CTL were screened for reactivity to the cervical carcinoma cell line C33A (HPV-, HLA-A2+) transfected with the HPV 16 E6 or E7 genes or the plasmid without insert. The CTL of 1 patient showed particularly strong CaSki and HPV E6 or E7 protein-specific cytotoxicity in a HLA-A2+-restricted fashion. In contrast, these CTL lysed neither a vector-only transfectant, the natural killer cell (NK) target, K562 nor the lymphokine-activated killer cell (LAK) target, Daudi. HLA-A2 restriction was demonstrated by the lack of recognition of a HLA-A2- CaSki cell line developed in our laboratory. The CTL line was cloned and 99 clones were harvested and screened; 51 clones lysed CaSki, of which 17 did not lyse the A2- CaSki. Of these HLA-A2- restricted clones, 8 did not lyse C33A transfectants, 6 lysed all C33A transfectants, 3 lysed C33A-E7 only and none lysed C33A-E6 only. These data imply that, within the bulk CTL line, HLA-A2-restricted recognition of antigens was restricted to CaSki antigens, antigens common to cervical carcinoma (CaSki plus C33A), or HPV-16-E7-derived antigen on the clonal level. The E7-restricted clones were negative for recognition of known HLA-A2-binding peptides from E7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • HLA-A2 Antigen / immunology*
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Lymphocyte Activation / immunology*
  • Molecular Sequence Data
  • Oncogene Proteins, Viral / immunology*
  • Oncogene Proteins, Viral / metabolism
  • Papillomaviridae / immunology*
  • Papillomavirus E7 Proteins
  • Repressor Proteins*
  • Sensitivity and Specificity
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / blood
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / virology*


  • E6 protein, Human papillomavirus type 16
  • HLA-A2 Antigen
  • Histocompatibility Antigens Class I
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Repressor Proteins
  • oncogene protein E7, Human papillomavirus type 16