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.
Schirmbeck
R
R
Institute for Medical Microbiology and Immunology, University of Ulm, Helmholtzstrasse 8/1, 89081, Ulm, Germany.
Melber
K
K
Reimann
J
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017951:Antigen Presentation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage* / Q000235:genetics / Q000502:physiology*; D007273:Injections, Intramuscular; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D006514:Hepatitis B Surface Antigens; D018664:Interleukin-12