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.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1136/gut.47.1.137
ISSNs: 0017-5749 (print)
1468-3288 (electronic)
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 > Clinical and Experimental Sciences
ePrint ID: 337529
Accepted Date and Publication Date:
July 2000Published
Date Deposited: 27 Apr 2012 12:48
Last Modified: 31 Mar 2016 14:26

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