title: Selection of conserved epitopes from hepatitis C virus for pan-populational stimulation of T-cell responses.
abstract: The hepatitis C virus (HCV) is able to persist as a chronic infection, which can lead to cirrhosis and liver cancer. There is evidence that clearance of HCV is linked to strong responses by CD8 cytotoxic T lymphocytes (CTLs), suggesting that eliciting CTL responses against HCV through an epitope-based vaccine could prove an effective means of immunization. However, HCV genomic plasticity as well as the polymorphisms of HLA I molecules restricting CD8 T-cell responses challenges the selection of epitopes for a widely protective vaccine. Here, we devised an approach to overcome these limitations. From available databases, we first collected a set of 245 HCV-specific CD8 T-cell epitopes, all known to be targeted in the course of a natural infection in humans. After a sequence variability analysis, we next identified 17 highly invariant epitopes. Subsequently, we predicted the epitope HLA I binding profiles that determine their potential presentation and recognition. Finally, using the relevant HLA I-genetic frequencies, we identified various epitope subsets encompassing 6 conserved HCV-specific CTL epitopes each predicted to elicit an effective T-cell response in any individual regardless of their HLA I background. We implemented this epitope selection approach for free public use at the EPISOPT web server.
authors.affiliation: Facultad de Medicina, Sección de Inmunología, Universidad Complutense de Madrid, Avenida Complutense S/N, 28040 Madrid, Spain.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Molero-Abraham
authors.affiliation: Facultad de Medicina, Sección de Inmunología, Universidad Complutense de Madrid, Avenida Complutense S/N, 28040 Madrid, Spain.
authors.forename: Esther M
authors.initials: EM
authors.lastname: Lafuente
authors.affiliation: School of Life and Health Sciences, University of Aston, Aston Triangle, Birmingham B4 7ET, UK.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Flower
authors.affiliation: Facultad de Medicina, Sección de Inmunología, Universidad Complutense de Madrid, Avenida Complutense S/N, 28040 Madrid, Spain.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Reche
mesh_terms: D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics; D064878:Web Browser
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D014764:Viral Proteins