Breaking tolerance in hepatitis B surface antigen (HBsAg) transgenic mice by vaccination with cross-reactive, natural HBsAg variants
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | European Journal of Immunology |
Volume | 33 |
Issue number | 12 |
Pages (from-to) | 3342-52 |
Number of pages | 10 |
ISSN | 0014-2980 |
DOIs | |
Publication status | Published - 2003 |
Bibliographical note
Keywords: Adoptive Transfer; Amino Acid Sequence; Animals; CD8-Positive T-Lymphocytes; Cell Line; Cross Reactions; Epitopes; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Immune Tolerance; Liver; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Sequence Data; Spleen; Vaccination
ID: 9943580