title: Mapping of immunodominant CD4+ T lymphocyte epitopes of hepatitis C virus antigens and their relevance during the course of chronic infection.
abstract: In acute and chronic viral disease the specific response of CD4+ T lymphocytes to certain viral proteins is an essential part of antiviral effector mechanisms. In hepatitis C virus infection, the contribution of the immune system and particularly of CD4+ T lymphocytes to the pathogenesis of disease is unknown. We serially determined the peripheral blood CD4+ T lymphocyte response to several recombinant hepatitis C virus proteins (core, NS3, NS4, NS5) and 17 overlapping synthetic peptides derived from the core sequence over up to 48 months in 43 patients with chronic hepatitis C; of these, 16 had been treated with interferon alfa (IFN). Twelve of 27 untreated patients, 4 of 4 sustained responders to IFN, 7 of 8 patients with a transient response, and 1 of 4 nonresponders showed a proliferative response to hepatitis C virus proteins. The hepatitis C virus core protein was the most immunogenic protein, and fine analysis with peptides indicated amino acids 23 to 42, 66 to 85, and 131 to 150 as immunodominant regions. In a subgroup of nine patients, proliferation assays were performed before or during IFN. In this subgroup, sustained responders but not those with a transient or no response to IFN showed a specific CD4+ immune reaction to hepatitis C viral antigens (P < .05). Infection with hepatitis C virus genotype 3a was significantly associated with a sustained response to IFN (P < .05). In general, a CD4+ T lymphocyte response was more common in patients with chronic hepatitis C who responded to interferon-alpha as compared with nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Institute for Immunology, University of Munich, Germany.
authors.forename: R M
authors.initials: RM
authors.lastname: Hoffmann
authors.forename: H M
authors.initials: HM
authors.lastname: Diepolder
authors.forename: R
authors.initials: R
authors.lastname: Zachoval
authors.forename: F M
authors.initials: FM
authors.lastname: Zwiebel
authors.forename: M C
authors.initials: MC
authors.lastname: Jung
authors.forename: S
authors.initials: S
authors.lastname: Scholz
authors.forename: H
authors.initials: H
authors.lastname: Nitschko
authors.forename: G
authors.initials: G
authors.lastname: Riethmüller
authors.forename: G R
authors.initials: GR
authors.lastname: Pape
mesh_terms: D000328:Adult; D000956:Antigens, Viral / Q000032:analysis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D002908:Chronic Disease; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000628:therapy; D006801:Humans; D016056:Immunodominant Epitopes; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D010455:Peptides / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D016056:Immunodominant Epitopes; D016898:Interferon-alpha; D010455:Peptides