Antibody and cytotoxic T-cell responses to soluble hepatitis B virus (HBV) S antigen in mice: implication for the pathogenesis of HBV-induced hepatitis.

Immune responses to components of hepatitis B virus (HBV) are assumed to play an essential role not only in the elimination of the virus but also in the pathogenesis of HBV-induced hepatitis. Protective humoral immunity to HBV is mediated by immune responses to HBV surface antigen (HBsAg). It is important to know which HBsAg preparations induce which type of cellular and humoral immune responses under which immunization conditions. We studied in BALB/c mice the humoral (antibody) response and the class I-restricted cytotoxic T-lymphocyte (CTL) response to different preparations of HBsAg particles: recombinant, small protein particles; plasma-derived, mixed particles formed by large, medium, and small surface proteins; and different preparations of recombinant, mixed particles formed by large and small surface proteins. Specific antibody levels appeared in the sera of immunized mice 2 to 3 weeks after immunization and were correlated with the antigen dose used for priming. HBsAg-specific antibody levels were enhanced by boost injections or by adsorbing the antigen to aluminum hydroxide. Injected in particulate form without adjuvants in the dose range of 0.1 to 10 micrograms per mouse, all HBsAg preparations tested efficiently primed specific CD8+ CTL of defined restriction and epitope specificity. Specific CTL reactivity was detectable from 5 days to more than 4 months postimmunization. In the dose range tested, it was independent of the antigen dose used for immunization and not enhanced by repeated boost injections. CTL were not elicited by HBsAg adsorbed to aluminum hydroxide. We have thus defined conditions under which HBsAg induced preferentially either a cellular immune response or a humoral immune response. These findings may be relevant for the interpretation of HBV-associated immunopathologic phenomena.