Production of interleukin-2 in response to synthetic peptides from hepatitis C virus E1 protein in patients with chronic hepatitis C: relationship with the response to interferon treatment

J Hepatol. 1996 Jul;25(1):1-9. doi: 10.1016/s0168-8278(96)80320-5.

Abstract

Background/aims: The role of cellular immunity in the clearance of hepatitis C virus after interferon therapy has not yet been elucidated. Here, we analyzed the T cell response to peptides from hepatitis C virus E1 protein in untreated and interferon-treated patients with chronic hepatitis C virus infection.

Methods: We used thirty-six 15-mer synthetic peptides from hepatitis C virus E1 protein (genotype 1a) in a sensitive interleukin-2 production assay in two groups of controls (healthy seronegative individuals and patients with liver diseases unrelated to hepatitis C virus), and three groups of patients with chronic hepatitis C: nine patients who cleared the virus after interferon treatment (group 1), nine patients who failed to respond to the therapy (group 2) and nine previously untreated patients (group 3).

Results: None of the controls responded to any of the peptides tested, whereas 8/9 (88%) of patients from group 1 responded positively. In contrast, only 2/9 (22%) of patients from group 2 showed peptide recognition. In group 3, 5/9 patients (55%) displayed positive response against E1 peptides. When E1 peptides from the sequence corresponding to genotype 1b (the commonest in patients who were non-responders to interferon) were tested in nine additional interferon-resistant patients (group 2*) a positive response was detected in only three of them (33%).

Conclusions: T cell recognition of hepatitis C virus E1 peptides in patients with chronic hepatitis C who exhibit sustained response to interferon therapy is increased as compared with interferon-resistant cases, suggesting that T cell immunity to hepatitis C virus structural proteins may play a role in the clearance of this viral infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • Chronic Disease
  • Female
  • Genotype
  • HLA-DR Antigens / analysis
  • Hepacivirus / classification
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Hepatitis C / immunology*
  • Hepatitis C / therapy
  • Humans
  • Interferon-alpha / therapeutic use*
  • Interleukin-2 / biosynthesis*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Peptide Fragments / immunology*
  • T-Lymphocytes / immunology*
  • Viral Envelope Proteins / immunology*

Substances

  • E1 protein, Hepatitis C virus
  • HLA-DR Antigens
  • Interferon-alpha
  • Interleukin-2
  • Peptide Fragments
  • Viral Envelope Proteins