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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

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
Authors
Issue Date2005
PublisherB M J Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/
Citation
Gut, 2005, v. 54 n. 1, p. 152-161 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/45372
ISSN
2015 Impact Factor: 14.921
2015 SCImago Journal Rankings: 6.474
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLin, CLen_HK
dc.contributor.authorTsai, SLen_HK
dc.contributor.authorLee, THen_HK
dc.contributor.authorChien, RNen_HK
dc.contributor.authorLiao, SKen_HK
dc.contributor.authorLiaw, YFen_HK
dc.date.accessioned2007-10-30T06:24:02Z-
dc.date.available2007-10-30T06:24:02Z-
dc.date.issued2005en_HK
dc.identifier.citationGut, 2005, v. 54 n. 1, p. 152-161en_HK
dc.identifier.issn0017-5749en_HK
dc.identifier.urihttp://hdl.handle.net/10722/45372-
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.en_HK
dc.format.extent410099 bytes-
dc.format.extent476510 bytes-
dc.format.mimetypeapplication/pdf-
dc.format.mimetypeapplication/pdf-
dc.languageengen_HK
dc.publisherB M J Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsGut. Copyright © B M J Publishing Group.en_HK
dc.subject.meshHepatitis-B,-Chronic-drug-therapyen_HK
dc.subject.meshLamivudine-therapeutic-useen_HK
dc.subject.meshReverse-Transcriptase-Inhibitors-therapeutic-useen_HK
dc.subject.meshT-Lymphocytes,-Cytotoxic-immunologyen_HK
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 Ben_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0017-5749&volume=54&issue=1&spage=152&epage=161&date=2005&atitle=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+Ben_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1136/gut.2003.032920en_HK
dc.identifier.pmid15591521-
dc.identifier.pmcidPMC1774356-
dc.identifier.scopuseid_2-s2.0-10844242136-
dc.identifier.isiWOS:000225659500028-

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