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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...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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2010
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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. |
format | Text |
id | pubmed-3012747 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
record_format | MEDLINE/PubMed |
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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