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.