Differential antigen-processing pathways of the hepatitis B virus e and core proteins

Background & Aims: Hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg) seem to play different roles In the induction and regulation of the antiviral immune response, although the two antigens share all major CD4(+) T-cell epitopes, and these epitopes can be processed from both antigenes via the exogenous anti-gen-presenting pathway. The aim of this study was to test the ability of antigen-presenting cells to present epitopes from endogenously synthesized MBcAg/HBeAg on HLA class II molecules. Methods: Lymphoblastoid cell lines infected with recombinant vaccinia viruses containing various HBcAg or HBeAg constructs and stable transfectants Were tested for their ability to stimulate HBcAg/HBeAg-specific CD4(+) T-cell clones. Results: Only antigen-presenting cells infected with HBeAg constructs but not those infected with HBcAg constructs were able to stimulate HBcAg/HBeAg-specific CD4(+) T-cell clones. T-cell activation by HBeAg constructs was completely inhibited by brefeldin A but not affected by chloroquin. In contrast, T-cell activation by exogenous, recombinant HBcAg was inhibited by chloroquin but not by brefeldin A. Conclusions:The findings indicate that processing and HLA class II-associated presentation df endogenously synthesized HBeAg in virus-infected cells, including hepatocytes, may occur. This mechanism may be involved in the regulation of the CD4(+) T-cell response to HBcAg/HBeAg.