The European searchable tumour line database

The European Searchable Tumour line Database (ESTDAB) () is a freely available and fully searchable database of melanoma-derived cell lines, which have been characterised for over 250 immunologically relevant markers by a consortium of European scientists. The database is linked to a cell bank, which can provide melanoma cell lines to non-profit investigators for a nominal handling charge. All cells are fully HLA typed at the genomic and surface expression levels. The expression of a number of surface antigens, apoptotic markers, tumour-associated antigens and extracellular matrix proteins has also been determined. Cytokine secretion has been tested and polymorphisms in cytokine genes have been identified. Glycans at the cell surface were identified and glycosyltransferase activity quantified. Cell lines with a particular constellation of these parameters can be sought online via the ESTDAB interface, which is included as part of the Immuno-Polymorphism Database (IPD) section of the European Bioinformatics Institute’s (EBI) website. This paper is a focussed research review from the meeting which took place on the 28th–29th May 2008 in Nottingham, UK, celebrating the contribution of Prof. I.A. “Tony” Dodi (29.1.2008) to the EU project “Network for the identification and validation of antigens and biomarkers in cancer and their application in clinical tumour immunology (ENACT).”     

Identification of three HLA-A*0201-restricted cytotoxic T cell epitopes in the cytomegalovirus protein pp65 that are conserved between eight strains of the virus.

The Ag specificity of the CTL response against CMV is directed almost entirely to a single CMV tegument protein, the phosphoprotein pp65. We report the identification of three peptides derived from the protein pp65 that displayed a high or intermediate binding to HLA-A*0201 molecules, which were also able to induce an in vitro CTL response in peripheral blood lymphocytes from CMV seropositive individuals. The peptide-specific CTLs generated were capable of recognizing the naturally processed pp65 either presented by CMV-infected cells or by cells infected with an adenovirus construct expressing pp65 in an HLA-A*0201-restricted manner. Thus, we were able to demonstrate responses to subdominant CTL epitopes in CMV-pp65 that were not detected in polyclonal cultures obtained by conventional stimulations. We also found that the amino acid sequences of the three peptides identified as HLA-A*0201-restricted CTL epitopes were conserved among different wild-type strains of CMV obtained from renal transplant patients, an AIDS patient, and a congenitally infected infant, as well as three laboratory strains of the virus (AD169, Towne and Davis). These observations suggest that these pp65 CTL peptide epitopes could potentially be used as synthetic peptide vaccines or for other therapeutic strategies aimed at HLA-A*0201-positive individuals, who represent approximately 40% of the European Caucasoid population. However, strain variation must be taken in consideration when the search for CTL epitopes is extended to other HLA class I alleles, because these mutations may span potential CTL epitopes for other HLA molecules, as it is described in this study.