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 polyprotein. Anti-HVR1 antibodies have been shown to protect against HCV infection, indicating that this region contains an important neutralization determinant. Recently we and others have demonstrated that HVR1 is also a T cell determinant able to activate helper T cell responses during HCV infection. In order to investigate the role of the immune response against HVR1 during HCV infection we have evaluated the humoral and lymphoproliferative responses to a panel of HVR1 peptides in HCV-infected patients with different outcomes of the disease following interferon-alpha (IFN-alpha) treatment. We observed that the frequency of anti-HVR1 T cell responses was significantly higher in patients who recovered after IFN-alpha therapy than in those who did not, while no differences in the anti-HVR1 antibody reactivities were detected. In addition, by generating HVR1-specific T cell lines and clones we identified human leukocyte-associated antigens DR4 restricted T cell epitopes in the carboxy-terminus of HVR1 and we demonstrated that broadly cross-reactive HVR1 T cells are elicited by HVR1.
Del Porto
P
P
Department of Cellular and Developmental Biology, University of Rome, "La Sapienza,", Rome, Italy.
Puntoriero
G
G
Scottà
C
C
Nicosia
A
A
Piccolella
E
E
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003001:Cloning, Molecular; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D014764:Viral Proteins / Q000276:immunology*
C400562:HVR1 protein, Hepatitis C virus; D016898:Interferon-alpha; D014764:Viral Proteins