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Single Chain Recombinant HLA-DQ2.5/peptide Molecules Block α2-gliadin-Specific Pathogenic CD4(+) T Cell Proliferation and Attenuate Production of Inflammatory Cytokines: A Potential Therapy for Celiac Disease

Celiac disease (CD) is a disorder of the small intestine caused by intolerance to wheat gluten and related proteins in barley and rye. CD4(+) T cells play a central role in CD, recognizing and binding complexes of HLA-DQ2.5 bearing gluten peptides that have survived digestion and that are deamidated...

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Detalles Bibliográficos
Autores principales: Huan, J, Meza-Romero, R, Mooney, J L, Vandenbark, A A, Offner, H, Burrows, G G
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012747/
https://www.ncbi.nlm.nih.gov/pubmed/20736999
http://dx.doi.org/10.1038/mi.2010.44
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author Huan, J
Meza-Romero, R
Mooney, J L
Vandenbark, A A
Offner, H
Burrows, G G
author_facet Huan, J
Meza-Romero, R
Mooney, J L
Vandenbark, A A
Offner, H
Burrows, G G
author_sort Huan, J
collection PubMed
description Celiac disease (CD) is a disorder of the small intestine caused by intolerance to wheat gluten and related proteins in barley and rye. CD4(+) T cells play a central role in CD, recognizing and binding complexes of HLA-DQ2.5 bearing gluten peptides that have survived digestion and that are deamidated by tissue transglutaminase (TG2), propagating a cascade of inflammatory processes that damage and eventually destroy the villous tissue structures of the small intestine. Here we present data showing that recombinant DQ2.5-derived molecules bearing covalently tethered α2-gliadin-61-71 peptide have a remarkable ability to block antigen-specific T cell proliferation and inhibited pro-inflammatory cytokine secretion in human DQ2.5-restricted α2-gliadin specific T cell clones obtained from patients with celiac disease. The results from our in vitro studies suggest that HLA-DQ2.5 derived molecules could significantly inhibit and perhaps reverse the intestinal pathology caused by T cell mediated inflammation and the associated production of proinflammatory cytokines.
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spelling pubmed-30127472011-07-01 Single Chain Recombinant HLA-DQ2.5/peptide Molecules Block α2-gliadin-Specific Pathogenic CD4(+) T Cell Proliferation and Attenuate Production of Inflammatory Cytokines: A Potential Therapy for Celiac Disease Huan, J Meza-Romero, R Mooney, J L Vandenbark, A A Offner, H Burrows, G G Mucosal Immunol Article Celiac disease (CD) is a disorder of the small intestine caused by intolerance to wheat gluten and related proteins in barley and rye. CD4(+) T cells play a central role in CD, recognizing and binding complexes of HLA-DQ2.5 bearing gluten peptides that have survived digestion and that are deamidated by tissue transglutaminase (TG2), propagating a cascade of inflammatory processes that damage and eventually destroy the villous tissue structures of the small intestine. Here we present data showing that recombinant DQ2.5-derived molecules bearing covalently tethered α2-gliadin-61-71 peptide have a remarkable ability to block antigen-specific T cell proliferation and inhibited pro-inflammatory cytokine secretion in human DQ2.5-restricted α2-gliadin specific T cell clones obtained from patients with celiac disease. The results from our in vitro studies suggest that HLA-DQ2.5 derived molecules could significantly inhibit and perhaps reverse the intestinal pathology caused by T cell mediated inflammation and the associated production of proinflammatory cytokines. 2010-08-25 2011-01 /pmc/articles/PMC3012747/ /pubmed/20736999 http://dx.doi.org/10.1038/mi.2010.44 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Huan, J
Meza-Romero, R
Mooney, J L
Vandenbark, A A
Offner, H
Burrows, G G
Single Chain Recombinant HLA-DQ2.5/peptide Molecules Block α2-gliadin-Specific Pathogenic CD4(+) T Cell Proliferation and Attenuate Production of Inflammatory Cytokines: A Potential Therapy for Celiac Disease
title Single Chain Recombinant HLA-DQ2.5/peptide Molecules Block α2-gliadin-Specific Pathogenic CD4(+) T Cell Proliferation and Attenuate Production of Inflammatory Cytokines: A Potential Therapy for Celiac Disease
title_full Single Chain Recombinant HLA-DQ2.5/peptide Molecules Block α2-gliadin-Specific Pathogenic CD4(+) T Cell Proliferation and Attenuate Production of Inflammatory Cytokines: A Potential Therapy for Celiac Disease
title_fullStr Single Chain Recombinant HLA-DQ2.5/peptide Molecules Block α2-gliadin-Specific Pathogenic CD4(+) T Cell Proliferation and Attenuate Production of Inflammatory Cytokines: A Potential Therapy for Celiac Disease
title_full_unstemmed Single Chain Recombinant HLA-DQ2.5/peptide Molecules Block α2-gliadin-Specific Pathogenic CD4(+) T Cell Proliferation and Attenuate Production of Inflammatory Cytokines: A Potential Therapy for Celiac Disease
title_short Single Chain Recombinant HLA-DQ2.5/peptide Molecules Block α2-gliadin-Specific Pathogenic CD4(+) T Cell Proliferation and Attenuate Production of Inflammatory Cytokines: A Potential Therapy for Celiac Disease
title_sort single chain recombinant hla-dq2.5/peptide molecules block α2-gliadin-specific pathogenic cd4(+) t cell proliferation and attenuate production of inflammatory cytokines: a potential therapy for celiac disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012747/
https://www.ncbi.nlm.nih.gov/pubmed/20736999
http://dx.doi.org/10.1038/mi.2010.44
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