Characterization of novel HLA-DR11-restricted HCV epitopes reveals both qualitative and quantitative differences in HCV-specific CD4+ T cell responses in chronically infected and non-viremic patients

Eur J Immunol. 2001 May;31(5):1438-46. doi: 10.1002/1521-4141(200105)31:5<1438::AID-IMMU1438>3.0.CO;2-2.


The CD4+ T cell response is of critical importance in determining the fate of many viral infections. Clearance of HCV has a strong association with the MHC class II antigen HLA-DR11 suggesting a key role for CD4+ T cells. We used an epitope-prediction program to identify multiple novel HLA-DR11-restricted epitopes derived from several HCV proteins. These epitopes then allowed us to explore the qualitative and quantitative aspects of specific CD4+ T cell responses in HLA-DR11+ patients. Irrespective of the time since viral clearance, all the non-viremic patients recognized four epitopes with a high frequency of IFN-gamma-producing memory CD4+ T cells. There appeared to be two subpopulations of memory cells, immediate "effector" memory cells (Th1 phenotype) and resting "central" memory cells (Th1/0). Chronically infected patients revealed an almost complete absence of HCV epitope-specific IFN-gamma-producing T cells. However, three of these epitopes induced IL-10 production (down-regulatory) raising the question as to whether these cells play a role in viral persistence. The frequency and phenotype of memory cells is likely to reflect the magnitude of the initial immune response, and suggests that a high frequency of IFN-gamma-secreting CD4+ T cells to multiple epitopes are important in clearance of HCV.

Publication types

  • Comparative Study

MeSH terms

  • Antigens, Viral / immunology*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-DR Antigens / immunology*
  • HLA-DR Serological Subtypes
  • Hepacivirus / immunology*
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / virology
  • Humans
  • Immunologic Memory / immunology
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-4 / metabolism
  • Ligands
  • Lymphocyte Count
  • Peptides / chemical synthesis
  • Peptides / immunology
  • Software
  • Viremia / immunology*
  • Viremia / virology


  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • HLA-DR Antigens
  • HLA-DR Serological Subtypes
  • HLA-DR11 antigen
  • Ligands
  • Peptides
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma