Induction of CTL responses and identification of a novel epitope of hepatitis B virus surface antigens in C57BL/6 mice immunized with recombinant vaccinia viruses

Abstract

MHC class I-restricted cytotoxic T lymphocyte (CTL) response to hepatitis B virus (HBV) surface antigens (HBsAg) has been suggested to play essential roles in viral clearance and pathogenesis of HBV-induced hepatitis. In the present study, we analyzed CTL responses to endogenously synthesized or exogenously introduced HBsAg in C57BL/6 mice (H-2 b). We show that the endogenously synthesized surface antigens of adr-type HBV encoded by recombinant vaccinia virus efficiently elicit CTL responses in C57BL/6 mice previously defined as non-responders to vaccinia-HBV immunization. We also show that two peptides, S 179–186 (FVQWFVGL) and S 208–216 (ILSPFLPLL), serve as effective motifs for CTL response in H-2 b system after in vitro restimulation of the primed T cells with either of the two synthetic peptides. S 208–215 has recently been identified as a CTL epitope which could be produced by exogenous pathway only, in contrast to the current result, while S 179–186 appeared a novel epitope for CTL response. In addition, we show that soluble HBsAg also elicits CTL responses in H-2 b mice upon in vitro restimulation with the two peptides, although less efficiently compared with the recombinant vaccinia viruses. These findings may provide an efficient experimental system for studying H-2 b-restricted immune responses against endogenously synthesized and exogenously introduced HBsAg.