Adjuvants that enhance priming of cytotoxic T cells to a Kb-restricted epitope processed from exogenous but not endogenous hepatitis B surface antigen

Intramuscular (i.m.) or s.c. injection of plasmid DNA encoding hepatitis B small surface antigen (HBsAg) primes potent MHC I-restricted cytotoxic T lymphocyte (CTL) responses in H-2(d) (BALB/c) and H-2(b) (C57BL/6) mice. In contrast, i.m. or s.c. injection of exogenous HBsAg particles without adjuvants primes CTL responses in 'high responder' H-2(d) but not 'low responder' H-2(b) mice. We have shown that processing of exogenous but not endogenous HBsAg generates the Kb-binding S208-215 peptide ILSPFLPL. This system allowed us to optimize conditions for stimulating murine CTL responses to exogenous antigen by identifying adjuvants that facilitate priming of Kb-restricted CTL by injecting recombinant HBsAg particles into 'low responder' H-2(b) mice. Synthetic oligodeoxynucleotides with immunostimulating sequences or the recombinant cytokine IL-12 efficiently enhanced priming of CTL to exogenous HBsAg. Hence, the adjuvanticity of DNA sequences that induce Th1 cytokines facilitate priming of MHC I-restricted T cell responses to exogenous antigen and are therefore of potential value in formulating vaccines designed to enhance CTL priming to exogenous antigen.