HLA-A26 restricted HCV-specific CD8+ T cell responses in acute and chronic HCV infection

Virus-specific CD8+ T cell responses play a major role in the antiviral immune response in hepatitis C virus (HCV) infection. In this context, it has recently been shown that the host Human Leukocyte Antigen (HLA) background plays a crucial role in the outcome of HCV infection. The HLA allele A26 is particularly interesting since it is one of the most frequent HLA alleles in Asia, present in up to 20% of the asian population and since it is associated with slow disease progression in human immunodeficiency virus (HIV) infection. Currently, there is no information available about the role of HLA-A26 in HCV infection, especially since no specific epitopes have been identified thus far. In this study, we describe the identification and characterisation of the first six HLA-A26 restricted HCV-specific CD8+ T cell epitopes. Consequently, HLA-A26 restricted HCV-specific CD8+ T cell responses have been studied in a cohort of acute resolving (three patients) and chronically HCV infected (sixteen patients) patients. Of note, the novel HLA-A26 restricted epitopes turned out to be immunodominant in acute resolving and chronically infected patients and were present both in the peripheral blood as well as the intrahepatic compartment. Viral sequence analysis of the targeted epitopes revealed that they are highly conserved in chronically infected patients, indicating the lack of viral escape mutations. Finally, the capacity of these epitopes to be immunogenic in the context of different HLA molecules was tested. Interestingly, we observed that these epitopes are recognized in a broad range of HLA class I molecules, suggesting degenerate immunogenicity even across supertype boundaries (e.g. HLA-A1 and HLA-A26). In sum, these findings shed light on the immunological meaning of HLA-A26 in HCV infection and have important implications for the future design of an epitope-based therapeutic vaccine.

Key words

HCV; HLA-A26; T cell response