Cytotoxic T lymphocyte responses and CTL epitope escape mutation in HBsAg, anti-HBe positive individuals
Khakoo, S.I., Ling, R., Scott, I., Dodi, A.I., Harrison, T.J., Dusheiko, G.M. and Madrigal, J.A. (2000) Cytotoxic T lymphocyte responses and CTL epitope escape mutation in HBsAg, anti-HBe positive individuals. Gut, 47, (1), 137-143. (doi:10.1136/gut.47.1.137). (PMID:10861276).
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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.
|Keywords:||hepatitis B virus, HLA, hepatitis B core antigen, cytotoxicity, mutant|
|Subjects:||Q Science > QR Microbiology > QR180 Immunology
Q Science > QR Microbiology > QR355 Virology
|Divisions:||Faculty of Medicine > Infection, Inflammation and Immunity
|Date Deposited:||27 Apr 2012 12:48|
|Last Modified:||27 Apr 2012 12:50|
|Contributors:||Khakoo, S.I. (Author)
Ling, R. (Author)
Scott, I. (Author)
Dodi, A.I. (Author)
Harrison, T.J. (Author)
Dusheiko, G.M. (Author)
Madrigal, J.A. (Author)
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