eprintid: 10102689
rev_number: 9
eprint_status: archive
userid: 695
dir: disk0/10/10/26/89
datestamp: 2020-06-25 13:00:25
lastmod: 2020-06-25 15:56:06
status_changed: 2020-06-25 13:00:25
type: thesis
metadata_visibility: show
creators_name: Khakoo, Salim Iqbal
title: Immunological and virological factors in chronic hepatitis B infection.
ispublished: unpub
note: Thesis digitised by ProQuest
abstract: The work of this thesis is a study of the virological and immunological characteristics of the chronic hepatitis B virus (HBV) carrier state. A study of viral load using a novel signal amplification assay (bDNA, Chiron Corporation, Emeryville, USA) in 71 subjects chronically infected with hepatitis B virus was performed. Seventy five percent of HBeAg positive and 39% of anti-HBe positive carriers were positive using this assay. The assay was more sensitive in the detection of serum HBV DNA than an in-house dot blot assay and more selective for patients requiring anti-viral therapy than nested PCR.

In order to subsequently study HLA class I restricted cytotoxic T lymphocyte (CTL) responses in the peripheral blood of HBV infected patients, a panel of dual transfectant target cell lines, derived from the L721.221 HLA-A, -B, -C null line was created which express a single HLA class I allele and the hepatitis B nucleocapsid antigen. These were used in a series of cytotoxicity assays and CTL responses demonstrated in one out of five HLA-A2 positive, three out of five HLA-B7 positive and one out two HLA-B35 positive carriers. In three out of three HLA-A2, -B7 positive individuals responses were only detected in the context of HLA-B7 and not HLA-A2, suggesting preferential recognition of the nucleocapsid antigen in the context of HLA-B7.

In a family of HLA-A68 positive chronic HBV carriers, CTL responses were detected in one out of three patients tested. Sequencing of the HBc141-151 HLA-A68 restricted CTL epitope in the virions of the family members demonstrated the presence of an arginine to cysteine substitution at the amino-terminus of the peptide in four of the anti-HBe positive affected siblings, but not the HBeAg positive carrier.

These data suggest that CTL responses are demonstrable in the peripheral blood of chronic HBV carriers, and that mutation in a CTL epitope is likely to be a consequence of this reactivity.
date: 1997
oa_status: green
full_text_type: other
thesis_class: doctoral_open
thesis_award: M.D.
language: eng
primo: open
primo_central: open_green
verified: verified_manual
full_text_status: public
pages: 192
institution: University College London
thesis_type: Doctoral
citation:        Khakoo, Salim Iqbal;      (1997)    Immunological and virological factors in chronic hepatitis B infection.                   Doctoral thesis  (M.D.), University College London.     Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10102689/1/Immunological_and_virological_.pdf