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Article: High frequency of functional anti-YMDD and -mutant cytotoxic T lymphocytes after in vitro expansion correlates with successful response to lamivudine therapy for chronic hepatitis B
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TitleHigh frequency of functional anti-YMDD and -mutant cytotoxic T lymphocytes after in vitro expansion correlates with successful response to lamivudine therapy for chronic hepatitis B
 
AuthorsLin, CL2
Tsai, SL3
Lee, TH1
Chien, RN1
Liao, SK1
Liaw, YF1
 
Issue Date2005
 
PublisherB M J Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/
 
CitationGut, 2005, v. 54 n. 1, p. 152-161 [How to Cite?]
DOI: http://dx.doi.org/10.1136/gut.2003.032920
 
AbstractBACKGROUND: Many determinants for a sustained response to lamivudine therapy have been reported but the role of T cell responsiveness remains unclear. The finding that tyrosine-methionine-aspartate-aspartate (YMDD) motif of the reverse transcriptase domain of hepatitis B virus (HBV) DNA polymerase carries a HLA-A2 restricted cytotoxic T lymphocyte (CTL) epitope makes quantitative measurement of the numbers of peptide specific CTLs feasible using MHC tetramer-peptide complex staining. AIM: To investigate the correlation between anti-YMDD motif CTL activity and the efficacy of lamivudine therapy in HLA-A2 positive patients with chronic hepatitis B (CH-B). METHODS: The function and phenotype of peptide and interleukin 2 expanded peripheral blood mononuclear cells were quantified by cell lytic assay and immunocytochemical analysis by staining with HLA-A2-peptide tetramer complexes. RESULTS: After in vitro expansion, sustained responders had more potent CTL responses against YMDD, YVDD, and YIDD, as well as other epitopes on HBV antigens than non-responders. The frequency of YMDD/YVDD/YIDD motif specific CTLs increased significantly with an effective cell lytic function during and after therapy in sustained responders but not in non-responders. YMDD specific CTLs cross reacted with YIDD and YVDD mutant epitopes, and shared T cell receptor gene usages with YIDD and YVDD specific CTLs. CONCLUSIONS: Sustained responders, at least HLA-A2 patients, elicited a more potent CTL immunity against YMDD and its mutants. YMDD specific CTLs are cross reactive with YVDD and YIDD mutant epitopes, which may further contribute to immune clearance of the mutant viruses and a successful response to lamivudine therapy in CH-B patients.
 
ISSN0017-5749
2013 Impact Factor: 13.319
 
DOIhttp://dx.doi.org/10.1136/gut.2003.032920
 
PubMed Central IDPMC1774356
 
ISI Accession Number IDWOS:000225659500028
 
DC FieldValue
dc.contributor.authorLin, CL
 
dc.contributor.authorTsai, SL
 
dc.contributor.authorLee, TH
 
dc.contributor.authorChien, RN
 
dc.contributor.authorLiao, SK
 
dc.contributor.authorLiaw, YF
 
dc.date.accessioned2007-10-30T06:24:02Z
 
dc.date.available2007-10-30T06:24:02Z
 
dc.date.issued2005
 
dc.description.abstractBACKGROUND: Many determinants for a sustained response to lamivudine therapy have been reported but the role of T cell responsiveness remains unclear. The finding that tyrosine-methionine-aspartate-aspartate (YMDD) motif of the reverse transcriptase domain of hepatitis B virus (HBV) DNA polymerase carries a HLA-A2 restricted cytotoxic T lymphocyte (CTL) epitope makes quantitative measurement of the numbers of peptide specific CTLs feasible using MHC tetramer-peptide complex staining. AIM: To investigate the correlation between anti-YMDD motif CTL activity and the efficacy of lamivudine therapy in HLA-A2 positive patients with chronic hepatitis B (CH-B). METHODS: The function and phenotype of peptide and interleukin 2 expanded peripheral blood mononuclear cells were quantified by cell lytic assay and immunocytochemical analysis by staining with HLA-A2-peptide tetramer complexes. RESULTS: After in vitro expansion, sustained responders had more potent CTL responses against YMDD, YVDD, and YIDD, as well as other epitopes on HBV antigens than non-responders. The frequency of YMDD/YVDD/YIDD motif specific CTLs increased significantly with an effective cell lytic function during and after therapy in sustained responders but not in non-responders. YMDD specific CTLs cross reacted with YIDD and YVDD mutant epitopes, and shared T cell receptor gene usages with YIDD and YVDD specific CTLs. CONCLUSIONS: Sustained responders, at least HLA-A2 patients, elicited a more potent CTL immunity against YMDD and its mutants. YMDD specific CTLs are cross reactive with YVDD and YIDD mutant epitopes, which may further contribute to immune clearance of the mutant viruses and a successful response to lamivudine therapy in CH-B patients.
 
dc.description.naturepublished_or_final_version
 
dc.format.extent410099 bytes
 
dc.format.extent476510 bytes
 
dc.format.mimetypeapplication/pdf
 
dc.format.mimetypeapplication/pdf
 
dc.identifier.citationGut, 2005, v. 54 n. 1, p. 152-161 [How to Cite?]
DOI: http://dx.doi.org/10.1136/gut.2003.032920
 
dc.identifier.doihttp://dx.doi.org/10.1136/gut.2003.032920
 
dc.identifier.isiWOS:000225659500028
 
dc.identifier.issn0017-5749
2013 Impact Factor: 13.319
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC1774356
 
dc.identifier.pmid15591521
 
dc.identifier.scopuseid_2-s2.0-10844242136
 
dc.identifier.urihttp://hdl.handle.net/10722/45372
 
dc.languageeng
 
dc.publisherB M J Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/
 
dc.rightsGut. Copyright © B M J Publishing Group.
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshHepatitis-B,-Chronic-drug-therapy
 
dc.subject.meshLamivudine-therapeutic-use
 
dc.subject.meshReverse-Transcriptase-Inhibitors-therapeutic-use
 
dc.subject.meshT-Lymphocytes,-Cytotoxic-immunology
 
dc.titleHigh frequency of functional anti-YMDD and -mutant cytotoxic T lymphocytes after in vitro expansion correlates with successful response to lamivudine therapy for chronic hepatitis B
 
dc.typeArticle
 
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<contributor.author>Chien, RN</contributor.author>
<contributor.author>Liao, SK</contributor.author>
<contributor.author>Liaw, YF</contributor.author>
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Author Affiliations
  1. Chang Gung University College of Medicine
  2. The University of Hong Kong
  3. Chi Mei Foundation Hospital