References
Query Results -- Details
MGI Accession ID: MGI:2683789
J Number: J:87140
Other Accession IDs:
Title: Breaking tolerance in hepatitis B surface antigen (HBsAg) transgenic mice by vaccination with cross-reactive, natural HBsAg variants.
Authors: Schirmbeck R; Dikopoulos N; Kwissa M; Leithauser F; Lamberth K; Buus S; Melber K; Reimann J
Journal: Eur J Immunol
Volume: 33
Issue: 12
Date: 2003 Dec
Year: 2003
Pages: 3342-52
Review Status: Peer Reviewed
Abstract:
Processing exogenous hepatitis B surface antigen (HBsAg) of the hepatitis B virus (HBV) generates the K(b)-binding S(208-215) epitope 1; processing endogenous HBsAg generates the K(b)-binding S(190-197) epitope 2. Cross-reactive CD8(+) T cell responses were primed to epitope 1 but not epitope 2 when mice were immunized with natural HBsAg(ayw), or HBsAg(adw2) variants differing within both epitopes by one or two residues. Expression of HBsAg(ayw) from a transgene in the liver renders (HBs-tg) mice tolerant to epitope 1 of HBsAg(ayw). CD8(+) T cells specific for epitope 1 could be primed in HBs-tg mice by HBsAg(adw2); these specific CD8(+) T cells cross-reacted with epitope 1 processed from the transgene-encoded HBsAg(ayw). The liver of vaccinated HBsAg(ayw) transgenic mice showed severe histopathology and contained functional (IFNgamma-producing), cross-reactive CD8(+) T cells, and vaccinated HBs-tg mice showed reduced antigenemia. Hence, vaccination with natural HBsAg variants from different HBV sero/genotypes can prime cross-reactive, specific CD8(+) T cell immunity that breaks tolerance to HBsAg.
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