1993 Fiscal Year Final Research Report Summary
Investigation of the Mechanism of Fulminant and Severe Hepatitis Correlated with Hepatitis B Virus Mutations
| Project/Area Number |
03454223
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | University of Tokyo (1992-1993)
Chiba University (1991) |
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Principal Investigator |
OMATA Masao University of Tokyo Second Department of Internal Medicine Professor, 医学部(病), 教授 (90125914)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMURA Masayuki University of Tokyo Second Department of Internal Medicine Fellow, 医学部(病), 医員
TADA Minoru University of Tokyo Second Department of Internal Medicine Fellow, 医学部(病), 医員
SHIRATORI Yasushi University of Tokyo Second Department of Internal Medicine Instructor, 医学部(病), 助手 (70196624)
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| Project Period (FY) |
1991 – 1993
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| Keywords | hepatitis B virus / core gene / mutation / wild type / HLA / hepatitis / fulminant |
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| Research Abstract |
Hepatitis B virus infection leads to a wide spectrum of liver injury, including self-limited acute hepatitis, fulminant hepatitis and chronic hepatitis with progression to cirrhosis or acute exacerbation to liver failure, as well as asymtomatic chronic carrier state. The hepatitis B core antigen could be an immunological target of cytotoxic T lymphocytes (CTL). To investigate the reason why the severe immunological attack occurs, the entire precore and core region was sequenced. No significant change in deduced amino acid residuewas noted in all the asymptomatic healthy carrires and all the self-limited acute hepatitis patients. In contrast, clustering changes in small segments of amino acids were found in all the patients with severe chronic liver disease and the fatal hepatitis cases. These data suggest that these regions with mutation may play an important role in the pathogenesis of hepatitis B viral disease, and such mutations are related to severe liver damage.
Recent studies revealed that the endogenously processed viral peptides bound to the class I human lymphocyte antigen (HLA) are recognized by CTLs and the size of the processed viral peptide could be as small as 9 amino acids. To study the mechanism how CTLs recognize HBV peptides bound to HLA Class I molecules, we have already established a method to separate HLA Class I molecules from hepatocytes using an affinity colum chromatography. We have started to analyze such peptides eluted from purified HLA class I molecules.
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