Relative immunogenicity of hepatitis B virus-encoded antigens as targets for cytotoxic T-cell response.
To analyse the immunological mechanism of hepatocellular injury in hepatitis B virus (HBV) infection, the immunoreactivity of HBV-encoded antigens as a target for cytotoxic T lymphocyte (CTL) response was examined using recombinant vaccinia virus (RVV) expressing surface protein (S), precore/core protein (PC), and core protein (C) of HBV. C3H/He mice (H-2k) were inoculated with each RVV. Their spleen cells were then harvested and stimulated in vitro with the histocompatible transfectant, which stably expressed hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core antigen (HBcAg), and used as effectors. As the targets, L cells (H-2k) infected with individual RVV were used. Cytotoxic test was performed with various combinations and ratios of effectors and targets. The reactivity of PC-primed effectors against PC-expressing targets was greatest with 71.4% specific lysis on average at an effector/target ratio of 12.5:1 among all the combinations. C-primed effectors against C-expressing target also revealed rather high cytotoxicity (specific lysis, 40.6% at an E/T ratio of 12.5:1). Furthermore, PC-primed and C-primed effectors showed a cross-reactivity to the targets expressing other nucleocapsid antigen, respectively. S-primed effectors showed less lytic activity against S-expressing targets (specific lysis, 18.4% at an E/T ratio of 12.5:1). The CTL responses were blocked by anti-CD8 and anti-major histocompatibility complex (MHC) class I antibodies, but not by anti-CD4 or anti-MHC class II. These findings suggest that endogenously synthesized nucleocapsid antigen, especially PC, is a dominant target for the MHC class I-restricted CTL in H-2k mice and that this system may work as an efficient model to study immunopathogenesis of HBV infection.
Ishikawa
T
T
Third Department of Internal Medicine, Nagoya University of Medicine, Japan.
Kakumu
S
S
Yoshioka
K
K
Yamada
M
M
Tanaka
K
K
Higashi
Y
Y
Takayanagi
M
M
Okumura
A
A
Kojima
A
A
Tamura
T
T
D000818:Animals; D001483:Base Sequence; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique; D005814:Genes, Viral; D006509:Hepatitis B / Q000276:immunology*; D006511:Hepatitis B Antigens / Q000032:analysis / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D006511:Hepatitis B Antigens