ArticleGut2005
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.
Article in Gut, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 24 citations in OpenAlex.
- A Systematic Review of T Cell Epitopes Defined from the Proteome of Hepatitis B Virus.Vaccines · 2022Review
- Screening and Identification of HBV Epitopes Restricted by Multiple Prevalent HLA-A Allotypes.Frontiers in immunology · 2022Article
- Rapid re-emergence of YMDD mutation of hepatitis B virus with hepatic decompensation after lamivudine retreatment.World journal of gastroenterology · 2008Article
- Simultaneous assessment of cytotoxic T lymphocyte responses against multiple viral infections by combined usage of optimal epitope matrices, anti- CD3 mAb T-cell expansion and "RecycleSpot"Journal of translational medicine · 2005Article
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMany 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.
aimTo 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).
methodsThe 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.
resultsAfter 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.
conclusionsSustained 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.