Determinants of HCV-specific CD8+ T cell expansion

摘要: Infection with the hepatitis C virus still remains a global health problem. The antiviral immune response against HCV by CD8+ T cells plays central role in viral containment, however, it has been highlighted numerous studies that cell responses during infection are relatively weak and dysfunctional. Activation of virus-specific is multi-step process, which sequence presented antigen, as well site antigen presentation important consequences for quality response. Hence, present thesis, determinants HCV-specific expansion were analyzed. HCV characterized high levels genetic variation between genotypes subtypes but also isolates same subtype. This immunodominant epitopes precludes protective immunity represents major obstacle to vaccine design. In this study, we analyzed diversity HLA-A*02-restricted epitope NS31406-1415 circulating genotype 1a 1b its impact on priming induction cross-reactive responses. Circulating variants showed distinct potential cross-reactivity patterns. Importantly, highest degree was induced rarely observed European population. Upon vaccination, elicited should be polyfunctional target multiple variants. study highlights relevance subsequent provides rational selection optimal HCV, associated broad response. A hallmark chronic infections hepatotropic viruses such notoriously cells. Primary encounter happens liver. It believed liver-specific environment can induce tolerance either dysfunctional or premature death activated Recent reports from mouse models indicate hepatocytes act antigen-presenting. Direct virally infected thus might inhibit response. This frequency after 10 days dramatically reduced presence hepatocytes. suppressive effect independent cell-type used antigen-presentation (hepatocyte PBMC) antigen-specific contact. Expansion almost completely restored transwell experiments indicating cell-contact dependent. Analysis cytokine profile culture supernatants revealed increased concentrations TGF-β compared their absence. This gives hints establishment viruses.