SELECTIVE STIMULATION OF MURINE CYTOTOXIC T-CELL AND ANTIBODY-RESPONSES BY PARTICULATE OR MONOMERIC HEPATITIS-B VIRUS SURFACE (S)-ANTIGEN

In the murine system, we tested in vivo the immunogenicity of differen t preparations of the yeast-derived surface antigen (S-antigen or S-pr otein) of hepatitis B virus (HBV). Native S-protein molecules self-ass emble into stable 22-nm particles. BALB/c mice immunized with low dose s of native S-particles without adjuvants efficiently generated an H-2 class I-restricted CD8(+) cytotoxic T lymphocyte (CTL) response, and developed easily detectable serum antibody titers against conformation al determinants of the native S-particle or linear epitopes of the den atured S-protein. Disruption of S-particles with sodium dodecyl sulfat e and beta-2-mercaptoethanol generated p24 S-monomers. Injection of an equal dose of S-monomers into mice efficiently primed CTL, but did no t stimulate an antibody response against conformational or linear epit opes of the native or denatured S-protein. In vivo priming of CTL by S -particles or S-monomers required ''endogenous'' processing of the ant igen because the injection of an equimolar (or higher) dose of an anti genic, S-derived 12-mer peptide into mice did not prime CTL. Native (p articulate) or denatured (monomeric) S-antigen injected with mineral o il (incomplete Freund's adjuvant) or aluminum hydroxide failed to stim ulate a CTL response. Hence? different preparations can be produced fr om a small protein antigen which specifically stimulate selected compa rtments of the immune system.