Selective stimulation of murine cytotoxic T cell and antibody responses by particulate or monomeric hepatitis B virus surface (S) antigen

Abstract

In the murine system, we tested in vivo the immunogenicity of different preparations of the yeast‐derived surface antigen (S‐antigen or S‐protein) of hepatitis B virus (HBV). Native S‐protein molecules self‐assemble into stable 22‐nm particles. BALB/c mice immunized with low doses 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 conformational determinants of the native S‐particle or linear epitopes of the denatured S‐protein. Disruption of S‐particles with sodium dodecyl sulfate and β‐2‐mercaptoethanol generated p24 S‐monomers. Injection of an equal dose of S‐monomers into mice efficiently primed CTL, but did not stimulate an antibody response against conformational or linear epitopes of the native or denatured S‐protein. In vivo priming of CTL by S‐particles or S‐monomers required “endogenous” processing of the antigen because the injection of an equimolar (or higher) dose of an antigenic, S‐derived 12‐mer peptide into mice did not prime CTL. Native (particulate) or denatured (monomeric) S‐antigen injected with mineral oil (incomplete Freund's adjuvant) or aluminum hydroxide failed to stimulate a CTL response. Hence, different preparations can be produced from a small protein antigen which specifically stimulate selected compartments of the immune system.