Dominant influence of an HLA-B27 restricted CD8+ T cell response in mediating HCV clearance and evolution.
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...
| Auteurs principaux: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Langue: | English |
| Publié: |
2006
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| _version_ | 1826298971836907520 |
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| author | Neumann-Haefelin, C McKiernan, S Ward, S Viazov, S Spangenberg, H Killinger, T Baumert, T Nazarova, N Sheridan, I Pybus, O von Weizsäcker, F Roggendorf, M Kelleher, D Klenerman, P Blum, H Thimme, R |
| author_facet | Neumann-Haefelin, C McKiernan, S Ward, S Viazov, S Spangenberg, H Killinger, T Baumert, T Nazarova, N Sheridan, I Pybus, O von Weizsäcker, F Roggendorf, M Kelleher, D Klenerman, P Blum, H Thimme, R |
| author_sort | Neumann-Haefelin, C |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T04:54:51Z |
| format | Journal article |
| id | oxford-uuid:d63b5fdc-ac2b-4ba8-b45d-399bdb139e4d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:54:51Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:d63b5fdc-ac2b-4ba8-b45d-399bdb139e4d2022-03-27T08:32:01ZDominant influence of an HLA-B27 restricted CD8+ T cell response in mediating HCV clearance and evolution.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d63b5fdc-ac2b-4ba8-b45d-399bdb139e4dEnglishSymplectic Elements at Oxford2006Neumann-Haefelin, CMcKiernan, SWard, SViazov, SSpangenberg, HKillinger, TBaumert, TNazarova, NSheridan, IPybus, Ovon Weizsäcker, FRoggendorf, MKelleher, DKlenerman, PBlum, HThimme, RVirus-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. |
| spellingShingle | Neumann-Haefelin, C McKiernan, S Ward, S Viazov, S Spangenberg, H Killinger, T Baumert, T Nazarova, N Sheridan, I Pybus, O von Weizsäcker, F Roggendorf, M Kelleher, D Klenerman, P Blum, H Thimme, R Dominant influence of an HLA-B27 restricted CD8+ T cell response in mediating HCV clearance and evolution. |
| title | Dominant influence of an HLA-B27 restricted CD8+ T cell response in mediating HCV clearance and evolution. |
| title_full | Dominant influence of an HLA-B27 restricted CD8+ T cell response in mediating HCV clearance and evolution. |
| title_fullStr | Dominant influence of an HLA-B27 restricted CD8+ T cell response in mediating HCV clearance and evolution. |
| title_full_unstemmed | Dominant influence of an HLA-B27 restricted CD8+ T cell response in mediating HCV clearance and evolution. |
| title_short | Dominant influence of an HLA-B27 restricted CD8+ T cell response in mediating HCV clearance and evolution. |
| title_sort | dominant influence of an hla b27 restricted cd8 t cell response in mediating hcv clearance and evolution |
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