Presence of hepatitis B surface antigen (HBsAg)-specific cytotoxic T cells in asymptomatic HBsAg carriers

To investigate whether there is any evidence of an immune stimulation against hepatitis B virus surface antigen (HBsAg) in asymptomatic HBsAg carriers, proliferative and cytotoxic re-sponses to HBsAg were measured in their peripheral blood lymphocytes. Although the majority of asymptomatic carriers had no proliferative response to HBsAg, 3 (25%) of 12 carriers showed significant T cell proliferation against HBsAg. In addition, using HBsAg-expressing autologous lymphoblastoid cell line (LCL) as target cells, HBsAg-specific cytotoxic activitywasfound in 2 of 3 asymptomatic HBsAg carriers who had a proliferative response against HBsAg. Furthermore, 6 cytotoxic T lymphocyte (CTL) clones were isolated from 1 asymptomatic carrier. The epitope recognized by 2 CTL clones was mapped to the major HBsAg residues158-172. These CTL clones were able to produce interferon-v, tumor necrosis factor-a, or granulocyte-macrophage colony-stimulating factor. These findings demonstrate the presence of HBsAg-specific, major histocompatibility complex class I-restricted CTL in asymptomatic HBsAg carriers. The mechanisms of how the hepatitis B virus (HBV) escapes immunologic surveillance and persists in chronic HBV surface antigen (HBsAg) carriers remain unclear