Functionally distinct T-cell epitopes within the hepatitis C virus non-structural 3 protein

Clearance of Hepatitis C Virus (HCV) infection is an uncommon phenomenon. T o understand the mechanism of viral persistence despite active cellular and humoral responses, we examined the in vitro cytokine response of PBMC from an HCV sero-positive, asymptomatic individual to recombinant intact antige n and sixty-nine overlapping peptides of the HCV non-structural (NS) 3 prot ein. Whereas, intact antigen induced strong proliferation and significant l evels of gamma IFN and IL-10, little or no IL-2 was produced. Only 7% of pe ptides induced IL-2, which also coincided with their ability to stimulate p roliferation. In contrast, 38% of the peptides induced gamma IFN while 35% induced IL-10. All IL-2 stimulating peptides also induced significant level s of gamma IFN and among these, a peptide corresponding to residues 358-375 was the strongest. In addition, 16% of the peptides induced both gamma IFN and IL-10. Exogenous recombinant IL-10 inhibited proliferation and IL-2 in duction in response to peptide 358-375. Furthermore, neutralization of IL-1 0 with an anti-IL-10 antibody resulted in enhanced IL-2 production in respo nse to recombinant NS3 protein. We suggest that IL-10 inducing epitopes wit hin HCV NS3 may thus down-regulate IL-2 dependent T-cell responses. Human I mmunology 60, 105-115 (1999). (C) American Society for Histocompatibility a nd Immunogenetics, 1999. Published by Elsevier Science Inc.