Interferon-γ is produced by CD8+ T cells in response to HLA-A24-restricted hepatitis C virus epitopes after sustained virus loss

Summary Differences in cytotoxic T lymphocyte activity in hepatitis C virus infection may account for the outcome of interferon monotherapy. To investigate this hypothesis, we analysed the response of peripheral CD8 + + + T cells that recognized epitopes presented by HLA-A*2402. We synthesized HLA/b 2- microglobulin/peptide complexes using two epitopes. Production of interferon-g by CD8 + + + T cells in response to plastic-bound monomeric HLA/ peptide complex was observed frequently in sustained virus responders (SVR) ( n = 13) against all the peptides, NS31296-1304 (the percentage of responding patients, 61·5%) and core 129-137 (53·8%), while no interferon-g production was observed in non-responders (NR) ( n = = = 13) for any of the peptides. Tet- ramer-staining showed the presence of CD8 + T cells specific for all the pep- tides except NS31296-1304 in two SVR at the end of interferon monotherapy, although hardly any such cells were found in four NR. Specific killing was observed against peptides NS31296-1304 (3/4) and core 129-137 (1/4) in sus- tained responders but none in non-responders. These results suggest that the responses of cytotoxic T lymphocytes (CTLs) were induced during interferon therapy in these patients and that interferon-g production by CD8 + + + T lym- phocytes against HCV NS31296-1304 and core 129-137 are well maintained in patients with SVR compared with those with NR. These findings emphasize the importance of the CD8 + T cell response in controlling HCV infection.