A helper T-cell antigen enhances generation of hepatitis C virus-specific cytotoxic T lymphocytes in vitro.
A T-cell helper for generation of hepatitis C virus-specific cytotoxic T lymphocytes was studied in three patients with chronic hepatitis C. In all three, human leukocyte antigen B44-restricted cytotoxic T lymphocytes recognizing an epitope in hepatitis C virus nucleocapsid protein residues 81-100 were generated from the peripheral blood lymphocytes by repeated stimulation with a synthetic hepatitis C virus nucleocapsid peptide. The proliferative response of peripheral blood lymphocytes to hepatitis C virus nucleocapsid protein residues 1-120 was observed in one patient, and was ascribed to CD4+ T cells. The helper T cells recognized a major epitope in residues 21-40 and a minor epitope(s) in residues 81-110. They produced interferon gamma, but interleukin 4 was not detectable in the T-helper cell culture supernatants. The hepatitis C virus nucleocapsid protein residues 1-120 and the major helper T-cell epitope enhanced generation of hepatitis C virus-specific cytotoxic T lymphocytes in vitro, although the protein alone did not generate them. In the other two patients, the protein did not enhance generation of hepatitis C virus-specific cytotoxic T lymphocytes in vitro. The results suggest that a hepatitis C virus-specific helper T-cell epitope is helpful for inducing a strong specific cytotoxic T-lymphocyte response.
Kita
H
H
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Moriyama
T
T
Kaneko
T
T
Hiroishi
K
K
Harase
I
I
Miura
H
H
Nakamura
I
I
Inamori
H
H
Kodama
T
T
Ohnishi
S
S
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000096:biosynthesis / Q000276:immunology*; D002213:Capsid / Q000276:immunology*; D016022:Case-Control Studies; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood; D000939:Epitopes; D015235:HLA-B Antigens / Q000145:classification / Q000276:immunology; D059948:HLA-B44 Antigen; D006526:Hepatitis C / Q000276:immunology*; D018936:Hepatitis C Antigens; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000956:Antigens, Viral; D016207:Cytokines; D000939:Epitopes; D015235:HLA-B Antigens; D059948:HLA-B44 Antigen; D018936:Hepatitis C Antigens; D010446:Peptide Fragments; D011994:Recombinant Proteins