A helper T‐cell antigen enhances generation of hepatitis C virus‐specific cytotoxic T lymphocytes in vitro

A T‐cell help 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 pep‐tide. 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 γ, 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. © 1995 Wiley‐Liss, Inc.