High prevalence of hypervariable region 1-specific and -cross-reactive CD4(+) T cells in HCV-infected individuals responsive to IFN-alpha treatment

The hypervariable region 1 (HVR1) of the putative envelope 2 protein of the hepatitis C virus (HCV) is the most variable part of the whole HCV polypro tein. Anti-HVR1 antibodies have been shown to protect against HCV infection , indicating that this region contains an important neutralization determin ant Recently we and others have demonstrated that HVR1 is also a T cell det erminant able to activate helper T cell responses during HCV infection. In order to investigate the role of the immune response against HVR1 during HC V infection we have evaluated the humoral and lymphoproliferative responses to a panel of HVR1 peptides in HCV-infected patients with different outcom es of the disease following interferon-alpha (IFN-alpha) treatment We obser ved that the frequency of anti-HVR1 T cell responses was significantly high er in patients who recovered after IFN-alpha therapy than in those who did not, while no differences in the anti-HVR1 antibody reactivities were detec ted. In addition, by generating HVR1-specific T cell lines and clones we id entified human leukocyte-associated antigens DR4 restricted T cell epitopes in the carboxy-terminus of HVR1 and we demonstrated that broadly cross-rea ctive HVR1 T cells are elicited by HVR1. (C) 2000 Academic Press.