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Cytotoxic T lymphocyte responses and CTL epitope escape mutation in HBsAg, anti-HBe positive individuals

Cytotoxic T lymphocyte responses and CTL epitope escape mutation in HBsAg, anti-HBe positive individuals
Cytotoxic T lymphocyte responses and CTL epitope escape mutation in HBsAg, anti-HBe positive individuals
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.
hepatitis B virus, HLA, hepatitis B core antigen, cytotoxicity, mutant
0017-5749
137-143
Khakoo, S.I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Ling, R.
55709ee3-3e36-4851-accc-245dbfdf8cd8
Scott, I.
c958e263-8892-41b7-82db-b4f1121fc8ea
Dodi, A.I.
50b5d50f-cc92-41cd-86cf-ab3ab532e215
Harrison, T.J.
6808f714-513a-4bb8-9c2b-806891b7a8a7
Dusheiko, G.M.
d38496da-e082-430c-b719-4230a4addc6c
Madrigal, J.A.
4cf54344-42e1-4411-b12a-80995b430395
Khakoo, S.I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Ling, R.
55709ee3-3e36-4851-accc-245dbfdf8cd8
Scott, I.
c958e263-8892-41b7-82db-b4f1121fc8ea
Dodi, A.I.
50b5d50f-cc92-41cd-86cf-ab3ab532e215
Harrison, T.J.
6808f714-513a-4bb8-9c2b-806891b7a8a7
Dusheiko, G.M.
d38496da-e082-430c-b719-4230a4addc6c
Madrigal, J.A.
4cf54344-42e1-4411-b12a-80995b430395

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)

Record type: Article

Abstract

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.

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More information

Published date: July 2000
Keywords: hepatitis B virus, HLA, hepatitis B core antigen, cytotoxicity, mutant
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337529
URI: http://eprints.soton.ac.uk/id/eprint/337529
ISSN: 0017-5749
PURE UUID: 9be84856-585c-43ac-ba6c-00f2affe2bed
ORCID for S.I. Khakoo: ORCID iD orcid.org/0000-0002-4057-9091

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Date deposited: 27 Apr 2012 12:48
Last modified: 15 Mar 2024 03:12

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Contributors

Author: S.I. Khakoo ORCID iD
Author: R. Ling
Author: I. Scott
Author: A.I. Dodi
Author: T.J. Harrison
Author: G.M. Dusheiko
Author: J.A. Madrigal

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