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.
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.
Godkin
A
A
Imperial College of Science, Technology and Medicine, St Mary's Hospital, London, GB. a.godkin@ic.ac.uk
Jeanguet
N
N
Thursz
M
M
Openshaw
P
P
Thomas
H
H
D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D059810:HLA-DR Serological Subtypes; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008024:Ligands; D018655:Lymphocyte Count; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D012984:Software; D014766:Viremia / Q000276:immunology* / Q000821:virology
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C080766:HLA-DR11 antigen; D008024:Ligands; D010455:Peptides; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma