Khakoo, SI and Ling, R and Scott, I and Dodi, AI and Harrison, TJ and Dusheiko, GM and Madrigal, JA (2000) Cytotoxic T lymphocyte responses and CTL epitope escape mutation in HBsAg, anti-HBe positive individuals. Gut , 47 (1) 137 - 143.
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BACKGROUND/AIMS: Clearance of hepatitis B virus (HBV) is characterised by a strong cytotoxic T cell response. Persistence of HBV in chronic hepatitis B carriers may be related to failure of this response. The aim of this study was to determine whether HLA class I restricted cytotoxic T lymphocyte (CTL) responses persist in anti-hepatitis B e (HBe) positive / HBV DNA negative individuals, and to correlate the presence of viral CTL epitope mutation with clinical outcome. METHODS: An HLA/HBV dual transfectant model was used to demonstrate these CTL responses in individuals chronically infected with HBV. Subsequently, a known hepatitis B core (HBc) CTL epitope was sequenced in a family of five chronically infected individuals all sharing a HLA allele (HLA- A68.1). RESULTS: Low level HLA class I restricted cytotoxic T cell responses were detected in the peripheral blood of five of eight anti- HBe positive individuals. In the family of HLA-A68.1 positive chronically infected individuals, mutation of the HLA-A68.1 restricted hepatitis B core antigen (HBcAg) CTL epitope STLPETTVVRR was found in all four anti-HBe positive individuals but not in the sole hepatitis B e antigen (HBeAg) positive patient. CONCLUSION: These data are consistent with a continued immune selection pressure on HBV in anti- HBe positive chronically infected individuals with low replicating HBV infection and suggest that mutation of a CTL epitope may be a consequence of the immune response, as opposed to the cause of viral persistence
|Title:||Cytotoxic T lymphocyte responses and CTL epitope escape mutation in HBsAg, anti-HBe positive individuals|
|Additional information:||UI - 20320796 LA - eng RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-A Antigens) RN - 0 (HLA-Aw68) RN - 0 (Hepatitis B Antibodies) RN - 0 (Hepatitis B Surface Antigens) RN - 0 (Hepatitis B e Antigens) RN - 0 (Histocompatibility Antigens Class I) PT - Journal Article DA - 20000726 IS - 0017-5749 SB - AIM SB - IM CY - ENGLAND JC - FVT|
|Keywords:||0 (Epitopes, 0 (Hepatitis B Antibodies), 0 (Hepatitis B e Antigens), 0 (Hepatitis B Surface Antigens), 0 (Histocompatibility Antigens Class I), 0 (HLA-A Antigens), 0 (HLA-Aw68), ADULT, allele, Amino Acid Sequence, analysis, antibodies, antibody, antigen, ANTIGENS, article, As, blood, Carrier State, carriers, CELL, Cell Culture, Cell Line, chemistry, Chronic, CHRONIC HEPATITIS, chronic hepatitis B, Class, CLASS I, CLASS-I, clinical, Core, CTL, Cytotoxic, cytotoxic T lymphocyte, cytotoxicity, DNA, E, ENGLAND, epitope, Epitopes, FAILURE, families, family, FEMALE, genetics, Hepatitis, hepatitis B, Hepatitis B Antibodies, Hepatitis B e Antigens, Hepatitis B Surface Antigens, Hepatitis B Virus, Histocompatibility, Histocompatibility Antigens Class I, HLA, HLA-A, HLA-A Antigens, IM, immune, IMMUNE RESPONSE, immune-response, Immunologic, immunology, individuals, INFECTED INDIVIDUALS, infection, LA, LEVEL, LONDON, Low, lymphocyte, LYMPHOCYTE RESPONSES, MALE, May, MED, medicine, Methods, Middle Age, model, Molecular Sequence Data, Mutation, Non-U.S.Gov't, Outcome, patient, peripheral, PERIPHERAL BLOOD, PERIPHERAL-BLOOD, positive, Pressure, response, RESPONSES, Result, selection, support, SURFACE, T cell, T lymphocyte, T-CELL, T-Lymphocyte, T-Lymphocyte), T-Lymphocytes, Transfection, UK, university, viral, VIRUS|
|UCL classification:||UCL > Pro-Provosts|
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