Dominant influence of an HLA-B27 restricted CD8+ T cell response in mediating HCV clearance and evolution

Hepatology. 2006 Mar;43(3):563-72. doi: 10.1002/hep.21049.


Virus-specific CD8+ T cell responses play an important role in the natural course of infection; however, the impact of certain CD8+ T cell responses in determining clinical outcome has not been fully defined. A well-defined cohort of women inoculated with HCV from a single source showed that HLA-B27 has a strong association with spontaneous clearance. The immunological basis for this association is unknown. However, the finding is especially significant because HLA-B27 has also been shown to have a protective role in HIV infection. We report the identification of an HLA-B27 restricted hepatitis C virus (HCV)-specific CD8+ T cell epitope that is recognized in the majority of recovered HLA-B27 positive women. In chronically HCV-infected individuals, analysis of the corresponding viral sequence showed a strong association between sequence variations within this epitope and expression of HLA-B27, indicating allele-specific selection pressure at the population level. Functional analysis in 3 chronically HCV-infected patients showed that the emerging variant viral epitopes represent escape mutations. In conclusion, our results suggest a dominant role of HLA-B27 in mediating spontaneous viral clearance as well as viral evolution in HCV infection and mechanistically link both associations to a dominant novel CD8+ T cell epitope. These results support the central role of virus-specific CD8+ T cells and the genetically determined restriction of the virus-specific T cell repertoire in HCV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD8-Positive T-Lymphocytes / immunology*
  • Epitopes, T-Lymphocyte / genetics*
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Genetic Predisposition to Disease
  • HLA-B27 Antigen / genetics
  • HLA-B27 Antigen / immunology*
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Hepatitis C / genetics
  • Hepatitis C / immunology*
  • Hepatitis C / virology
  • Humans
  • Immunity, Cellular
  • Male
  • Middle Aged


  • Epitopes, T-Lymphocyte
  • HLA-B27 Antigen