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Selection of high‐avidity CD8 T cells correlates with control of hepatitis C virus infection
Author(s) -
Neveu Bérangère,
Debeaupuis Emilie,
Echasserieau Klara,
le MoullacVaidye Béatrice,
Gassin Michelle,
Jegou Loïg,
Decalf Jérémie,
Albert Matthew,
Ferry Nicolas,
Gournay Jérôme,
Houssaint Elisabeth,
Bonneville Marc,
Saulquin Xavier
Publication year - 2008
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.22379
Subject(s) - avidity , cytotoxic t cell , immunology , virology , biology , hepatitis c virus , cd8 , epitope , t cell receptor , t cell , serology , antigen , human leukocyte antigen , virus , antibody , immune system , in vitro , biochemistry
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‐γ), 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‐γ 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. (H EPATOLOGY 2008.)