HLA-A2-restricted peripheral blood cytolytic T lymphocyte response to HPV type 16 proteins E6 and E7 from patients with neoplastic cervical lesions |
| |
Authors: | Carys Evans Stefan Bauer Thomas Grubert Cosima Brucker Sigfried Baur Klaus Heeg Hermann Wagner G B Lipford |
| |
Institution: | (1) Institute for Medical Microbiology, Technical University of Munich, Trogerstrasse 32, 81675 Munich, Germany, DE;(2) I. Women’s Hospital, Ludwig-Maximilians University, Munich, Germany (Fax: +49 89 4140 4942), DE |
| |
Abstract: | 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.
Received: 16 November 1995 / Accepted: 15 January 1996 |
| |
Keywords: | Cytolytic T cell Human papillomavirus type 16 HLA-A2 Cervical intraepithelial neoplasia CaSki cell line |
本文献已被 SpringerLink 等数据库收录! |
|