Cytotoxic T-cell responses to the nucleocapsid proteins of HBV in chronic hepatitis: evidence that antibody modulation may cause protracted infection

The nucleocapsid antigens (HBc and HBe) are present on the membranes of HBV-infected hepatocytes from HBV carriers. In autologous cytotoxicity experiments we demonstrate that cytotoxic T cells sensitised to the nucleocapsid proteins of hepatitis B are present in HBe antigen-positive HBV carriers with chronic hepatitis and can be blocked by monoclonal anti-HBc and anti-HBe. Passive immunisation of chimpanzees with monoclonal anti-HBc and anti-HBe offers no protection against HBV infection but in both cases leads to an unusually prolonged hepatitis probably by modulation of HBc and HBe antigen display on the hepatocytes. High-titre anti-HBc in the circulation of HBe antigen-positive patients probably modulates the former protein making HBe the important target antigen for cytotoxic T cells mediating liver damage in chronic carriers. These data also support the hypothesis that passive transfer of IgG anti-HBc across the placenta may be one major factor promoting development of persistent infection in neonates infected from carrier mothers.