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Dominant influence of an HLA‐B27 restricted CD8+ T cell response in mediating HCV clearance and evolution
Author(s) -
NeumannHaefelin Christoph,
McKiernan Susan,
Ward Scott,
Viazov Sergei,
Spangenberg Hans Christian,
Killinger Thomas,
Baumert Thomas F.,
Nazarova Natalja,
Sheridan Isabelle,
Pybus Oliver,
von Weizsäcker Fritz,
Roggendorf Michael,
Kelleher Dermot,
Klenerman Paul,
Blum Hubert E.,
Thimme Robert
Publication year - 2006
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21049
Subject(s) - epitope , virology , immunology , cd8 , biology , hepatitis c virus , virus , population , human leukocyte antigen , t cell , cytotoxic t cell , immune system , antibody , antigen , medicine , genetics , environmental health , in vitro
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. (H EPATOLOGY 2006;43:563–572.)