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

Background & Aims: Hepatitis B e antigen (HBeAg) and hepatitis B core antig en (HBcAg) seem to play different roles In the induction and regulation of the antiviral immune response, although the two antigens share all major CD 4(+) T-cell epitopes, and these epitopes can be processed from both antigen es 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 e ndogenously synthesized MBcAg/HBeAg on HLA class II molecules. Methods: Lym phoblastoid cell lines infected with recombinant vaccinia viruses containin g various HBcAg or HBeAg constructs and stable transfectants Were tested fo r their ability to stimulate HBcAg/HBeAg-specific CD4(+) T-cell clones. Res ults: Only antigen-presenting cells infected with HBeAg constructs but not those infected with HBcAg constructs were able to stimulate HBcAg/HBeAg-spe cific CD4(+) T-cell clones. T-cell activation by HBeAg constructs was compl etely inhibited by brefeldin A but not affected by chloroquin. In contrast, T-cell activation by exogenous, recombinant HBcAg was inhibited by chloroq uin but not by brefeldin A. Conclusions:The findings indicate that processi ng and HLA class II-associated presentation df endogenously synthesized HBe Ag in virus-infected cells, including hepatocytes, may occur. This mechanis m may be involved in the regulation of the CD4(+) T-cell response to HBcAg/ HBeAg.