Selection of Conserved Epitopes from Hepatitis C Virus for Pan-Populational Stimulation of T-Cell Responses. (21st November 2013)

• Record Type: Journal Article
• Authors: Molero-Abraham, Magdalena; Lafuente, Esther M.; Flower, Darren R.; Reche, Pedro A.
• Other Names: Fridkis-Hareli Masha Academic Editor.
• Is Part Of: Clinical & developmental immunology. Volume 2013(2013)
• Publication Date: 2013-11-21
• Subjects: Developmental immunology -- Periodicals; Clinical immunology -- Periodicals; Immune System -- immunology -- Periodicals; Immune System -- growth & development -- Periodicals; Immune System Diseases -- immunology -- Periodicals; 571.9638
• DOI: 10.1155/2013/601943
• Languages: English
• ISSNs: 1740-2522

Abstract

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.