Interferon gamma production by peripheral blood lymphocytes to hepatitis C virus core protein in chronic hepatitis C infection.
Evidence suggests that cellular immunity to hepatitis C virus (HCV) core protein may be important in the pathogenesis of viral infection. Therefore, interferon gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) derived from patients with chronic HCV infection (genotype 1b) was examined. The cellular immune response was evaluated with a recombinant HCV core fusion protein derived from a patient with genotype 1b. To identify the immunodominant epitopes, IFN-gamma production in responders was also assessed with a panel of nine synthetic peptides that covered the entire core region. It was found that mononuclear cells from 24 (52%) of 46 patients with chronic liver disease responded to the core protein; asymptomatic HCV carriers demonstrated a lower response rate (14%, P < .05). More important, individuals who had received IFN-alpha treatment and went into clinical and virological remission had a higher response rate (75%, P < .05) compared with those with ongoing hepatitis whose treatment failed (31%). Of 25 patients whose mononuclear cells responded to HCV core protein, 18 had a significant response to one or more peptides; 12 patients reacted to a peptide mixture containing hydrophilic sequences. The core peptide amino acid sequence 141 to 160 was recognized in 9 patients. Interestingly, 7 of 8 patients bearing HLA DR 4 and w53 haplotypes recognized the peptide sequence 141 to 160. Thus, IFN-gamma production of the mononuclear cell response appeared to be HLA DR restricted, and the responding cells were identified as CD4+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Iwata
K
K
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Wakita
T
T
Okumura
A
A
Yoshioka
K
K
Takayanagi
M
M
Wands
J R
JR
Kakumu
S
S
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D002908:Chronic Disease; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007564:Japan; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D006684:HLA-DR Antigens; D018936:Hepatitis C Antigens; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D007371:Interferon-gamma; D005982:Glutathione Transferase