Immunobiology and pathogenesis of hepatocellular injury in hepatitis B virus transgenic mice.
The role of the immune response to hepatitis B virus (HBV)-encoded antigens in the pathogenesis of liver cell injury has not been defined because of the absence of appropriate experimental models. HBV envelope transgenic mice were used to show that HBV-encoded antigens are expressed at the hepatocyte surface in a form recognizable by major histocompatibility complex (MHC) class I-restricted, CD8+ cytotoxic T lymphocytes specific for a dominant T cell epitope within the major envelope polypeptide and by envelope-specific antibodies. Both interactions led to the death of the hepatocyte in vivo, providing direct evidence that hepatocellular injury in human HBV infection may also be immunologically mediated.
Research Institute of Scripps Clinic, La Jolla, CA 92037.
T
T
Moriyama
S
S
Guilhot
K
K
Klopchin
B
B
Moss
C A
CA
Pinkert
R D
RD
Palmiter
R L
RL
Brinster
O
O
Kanagawa
F V
FV
Chisari
D000595:Amino Acid Sequence; D000818:Animals; D002461:Cell Line, Transformed; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D006509:Hepatitis B / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008099:Liver / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D013539:Simian virus 40; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014162:Transfection
D000939:Epitopes; D006514:Hepatitis B Surface Antigens; D015395:Histocompatibility Antigens Class I