Major Histocompatibility Complex (MHC) Expression and Antigen Presentation in Cervical Cancer

Abstract

The strong association between the presence of certain oncogenic types of papilloma-virus and the development of cervical. cancer has implicated these viruses in the progression of this disease. Human papillomavirus (HPV) types 16 and 18 are most frequently found associated with high grade cervical. intraepithelial. neoplasia (CIN) lesions and invasive carcinomas of the cervix. The expression of specific viral. proteins through the various stages of the natural. history of cervical. cancer may evoke immunological. consequences of relevance to the progression or regression of this disease. Evidence in support of an active role for the immune system in preventing the development of HPV associated malignancies has come from immunocompromised individuals including allograft recipients, cancer and AIDS patients who often exhibit an increased incidence of HPV associated lesions (eg. Halpert et al., 1985). The recognition of antigen by T cells is restricted by the polymorphic products of the MHC whose function is to present short peptides at the cell surface for T cell surveillance. Therefore the expression of HLA and the normal. functioning of the peptide processing and transport machinery are crucial. factors in the potential. recognition of virally infected cells (Neefjes and Ploegh, 1992; Monaco, 1992). This article reviews our work on the expression of polymorphic MHC class I and II antigens in premalignant and malignant lesions of the cervix. To discover whether HPV derived antigens can be presented for immune recognition, specific MHC-bound peptides have been identified, isolated and sequenced from cells expressing HPV 16 transforming proteins. This approach offers an alternative route towards identifying putative T cell epitopes. There is the potential. for identification of tumour specific antigens of any origin if a cytotoxic T lymphocyte (CTL) line and a corresponding tumour target are available. Fractionated peptides derived from a tumour cell line can be presented on autologous lymphoblastoid cells as targets for the tumour specific CTL, (derived for example from associated infiltrating T lymphocytes; see Ghosh et al., this volume) and the specific peptide sequenced.