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

✍ Scribed by Bérangère Neveu; Emilie Debeaupuis; Klara Echasserieau; Béatrice le Moullac-Vaidye; Michelle Gassin; Loïg Jegou; Jérémie Decalf; Matthew Albert; Nicolas Ferry; Jérôme Gournay; Elisabeth Houssaint; Marc Bonneville; Xavier Saulquin

• Book ID: 102849659
• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 784 KB
• Volume: 48
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.22379

✦ Synopsis

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.