Immune response of peripheral blood mononuclear cells to HBx-antigen of hepatitis B virus

✍ Scribed by Maria-Christina Jung; Marietta Stemler; Thomas Weimer; Ulrich Spengler; Jutta Döhrmann; Robert Hoffmann; Dieter Eichenlaub; Josef Eisenburg; Gustav Paumgartner; Gert Riethmüller; Hans Will; Gerd R. Pape

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 732 KB
• Volume: 13
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840130405

✦ Synopsis

The hepatitis B virus genome encodes a transcriptional transactivator protein designated HBxAg. We have investigated whether this antigen is a target structure for human T-lymphocytes. Using recombinant HBxAg protein, we found HBxAg-specific stimulation of peripheral blood mononuclear cells in patients with acute hepatitis B virus infection (6 of 6) and chronic hepatitis B virus infection (6 of 17) but not in healthy individuals. With HBxAg-specific synthetic polypeptides, several T-cell epitopes were identified. Most were located in the carboxyterminal half of the HBxAg protein. Five T-cell clones specific for a T-cell epitope located at the carboxyterminal region of HBxAg were established and found to belong to the CD2/CD4-positive, CDS-negative subtype. These data establish for the first time HBxAg as an antigen in the cellular immune response. (HEPATOLOGY 1991;13:637-643.)

Human HBV infection still represents one of the major world health problems and its sequelae range from inapparent infection and acute and chronic hepatitis to hepatic cirrhosis and the development of liver cancer (1). Some of the pathogenic features, including the development of liver cell carcinoma, are also seen in the infection of animals with related viruses (2). HBVs, which belong to the hepadnavirus family, are not cytopathogenic, and therefore immune response mechanisms of the infected host are believed to determine the outcome of infection (3, 4).

Thus far, the roles of viral structural proteins and derivatives thereof have been analyzed as antigens for B-cell and T-cell responses. The humoral and cellular immune response to HBsAg, pre-S1Ag and pre-S2Ag and to HBcAg and HBeAg has been investigated in some detail (5)(6)(7)(8)(9)(10)(11). For two known nonstructural proteins,