Source:http://linkedlifedata.com/resource/pubmed/id/16496339
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rdf:type | |
lifeskim:mentions |
umls-concept:C0015219,
umls-concept:C0019740,
umls-concept:C0039194,
umls-concept:C0085358,
umls-concept:C0086597,
umls-concept:C0220847,
umls-concept:C0443288,
umls-concept:C0449297,
umls-concept:C0871261,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1527180,
umls-concept:C1704632,
umls-concept:C1706438,
umls-concept:C1706817,
umls-concept:C2698600,
umls-concept:C2911692
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pubmed:issue |
3
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pubmed:dateCreated |
2006-4-3
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pubmed:abstractText |
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.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0270-9139
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pubmed:author |
pubmed-author:BaumertThomas FTF,
pubmed-author:BlumHubert EHE,
pubmed-author:KelleherDermotD,
pubmed-author:KillingerThomasT,
pubmed-author:KlenermanPaulP,
pubmed-author:McKiernanSusanS,
pubmed-author:NazarovaNataljaN,
pubmed-author:Neumann-HaefelinChristophC,
pubmed-author:PybusOliverO,
pubmed-author:RoggendorfMichaelM,
pubmed-author:SheridanIsabelleI,
pubmed-author:SpangenbergHans ChristianHC,
pubmed-author:ThimmeRobertR,
pubmed-author:ViazovSergeiS,
pubmed-author:WardScottS,
pubmed-author:von WeizsäckerFritzF
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pubmed:issnType |
Print
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
563-72
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pubmed:dateRevised |
2007-8-13
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pubmed:meshHeading |
pubmed-meshheading:16496339-Adult,
pubmed-meshheading:16496339-Aged,
pubmed-meshheading:16496339-CD8-Positive T-Lymphocytes,
pubmed-meshheading:16496339-Epitopes, T-Lymphocyte,
pubmed-meshheading:16496339-Female,
pubmed-meshheading:16496339-Genetic Predisposition to Disease,
pubmed-meshheading:16496339-HLA-B27 Antigen,
pubmed-meshheading:16496339-Hepacivirus,
pubmed-meshheading:16496339-Hepatitis C,
pubmed-meshheading:16496339-Humans,
pubmed-meshheading:16496339-Immunity, Cellular,
pubmed-meshheading:16496339-Male,
pubmed-meshheading:16496339-Middle Aged
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pubmed:year |
2006
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pubmed:articleTitle |
Dominant influence of an HLA-B27 restricted CD8+ T cell response in mediating HCV clearance and evolution.
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pubmed:affiliation |
Department of Medicine II, University of Freiburg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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