Definition of hepatitis B virus (HBV)-specific target antigens recognized by cytotoxic T cells in acute HBV infection.

We have investigated the specificity of cell-mediated cytotoxicity for autologous liver cells in 10 patients with acute hepatitis B in relation to the expression of hepatitis B virus (HBV) antigens and IgG on the surface of hepatocytes. Hepatitis B core antigen (HBcAg) was expressed on hepatocytes from six patients and hepatitis B surface antigen (HBcAG) from four, though always in association with HBcAg. Peripheral blood mononuclear cells (PBMC) were significantly cytotoxic in eight of the patients, and fractionation experiments revealed that the cytotoxic effect was equally mediated by T and non-T cells. Monoclonal antibody blocking experiments showed that HBcAg was the major target antigen recognized by T cells, although some inhibition of cytotoxicity was observed after pretreatment of target cells with monoclonal anti-HBs in patients with liver cell surface HBsAg. In contrast, non-T cells were not consistently inhibited by either monoclonal anti-HBc or anti-HBs. These findings further suggest that the HBV nucleoprotein serves as a target for recognition by cytotoxic T cells.