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Selection of high-avidity CD8 T cells correlates with control of hepatitis C virus infection

Abstract : Both strong antigenic avidity and acquisition of proper effector functions contribute to the efficacy of antiviral T cell responses. To correlate these parameters with the outcome of hepatitis C virus (HCV) infection, we characterized HCV-specific CD8 T cell lines isolated after immunomagnetic sorting of peripheral blood mononuclear cells from human leukocyte antigen A*02 (HLA-A*02) individuals with various HCV serological statuses, using recombinant HLA-A*0201 multimers loaded with three immunodominant HCV genotype 1-derived epitopes. CD8 T cells specific for these three epitopes were derived from most HLA-A*0201 individuals, regardless of their HCV serology or clinical outcome. Donors recovered from genotype 1 HCV infection were enriched for high-avidity T cells with enhanced interferon gamma (IFN-gamma), tumor necrosis factor alpha, and cytotoxic T lymphocyte responses, when compared with seronegative donors and seropositive patients infected with irrelevant HCV genotypes. Patients chronically infected with genotype 1 strain yielded almost exclusively low-avidity T cells, whose hyporesponsiveness was primarily attributable to low T cell receptor (TCR) avidity rather than intrinsic functional defects. CONCLUSION: This study suggests that strong IFN-gamma responses associated with efficient viral clearance primarily result from Ag-driven selection/survival of HCV-specific T cells expressing high-avidity TCR. It also suggests a link between the quality of the initial HCV-specific T cell repertoire and susceptibility to chronic infection.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01402305
Contributor : Marie-Christine Vougny <>
Submitted on : Thursday, November 24, 2016 - 3:02:58 PM
Last modification on : Friday, June 19, 2020 - 3:08:50 AM

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Bérangère Neveu, Emilie Debeaupuis, Klara Echasserieau, Béatrice Le Moullac-Vaidye, Michelle Gassin, et al.. Selection of high-avidity CD8 T cells correlates with control of hepatitis C virus infection. Hepatology, Wiley-Blackwell, 2008, 48 (3), pp.713 - 722. ⟨10.1002/hep.22379⟩. ⟨pasteur-01402305⟩

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