Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease.
Celiac disease is a genetic condition that results in a debilitating immune reaction in the gut to antigens in grain. The antigenic peptides recognized by the T cells that cause this disease are incompletely defined. Our understanding of the epitopes of pathogenic CD4(+ )T cells is based primarily o...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2010
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| _version_ | 1826262574954446848 |
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| author | Tye-Din, J Stewart, J Dromey, J Beissbarth, T van Heel, D Tatham, A Henderson, K Mannering, S Gianfrani, C Jewell, D Hill, A McCluskey, J Rossjohn, J Anderson, R |
| author_facet | Tye-Din, J Stewart, J Dromey, J Beissbarth, T van Heel, D Tatham, A Henderson, K Mannering, S Gianfrani, C Jewell, D Hill, A McCluskey, J Rossjohn, J Anderson, R |
| author_sort | Tye-Din, J |
| collection | OXFORD |
| description | Celiac disease is a genetic condition that results in a debilitating immune reaction in the gut to antigens in grain. The antigenic peptides recognized by the T cells that cause this disease are incompletely defined. Our understanding of the epitopes of pathogenic CD4(+ )T cells is based primarily on responses shown by intestinal T-cells in vitro to hydrolysates or polypeptides of gluten, the causative antigen. A protease-resistant 33-amino acid peptide from wheat alpha-gliadin is the immunodominant antigen, but little is known about the spectrum of T cell epitopes in rye and barley or the hierarchy of immunodominance and consistency of recognition of T-cell epitopes in vivo. We induced polyclonal gluten-specific T cells in the peripheral blood of celiac patients by feeding them cereal and performed a comprehensive, unbiased analysis of responses to all celiac toxic prolamins, a class of plant storage protein. The peptides that stimulated T cells were the same among patients who ate the same cereal, but were different after wheat, barley and rye ingestion. Unexpectedly, a sequence from omega-gliadin (wheat) and C-hordein (barley) but not alpha-gliadin was immunodominant regardless of the grain consumed. Furthermore, T cells specific for just three peptides accounted for the majority of gluten-specific T cells, and their recognition of gluten peptides was highly redundant. Our findings show that pathogenic T cells in celiac disease show limited diversity, and therefore suggest that peptide-based therapeutics for this disease and potentially other strongly HLA-restricted immune diseases should be possible. |
| first_indexed | 2024-03-06T19:38:22Z |
| format | Journal article |
| id | oxford-uuid:1fcd70f9-d7f2-4e9c-b4b1-e3c99e82e82d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:38:22Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:1fcd70f9-d7f2-4e9c-b4b1-e3c99e82e82d2022-03-26T11:24:06ZComprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1fcd70f9-d7f2-4e9c-b4b1-e3c99e82e82dEnglishSymplectic Elements at Oxford2010Tye-Din, JStewart, JDromey, JBeissbarth, Tvan Heel, DTatham, AHenderson, KMannering, SGianfrani, CJewell, DHill, AMcCluskey, JRossjohn, JAnderson, RCeliac disease is a genetic condition that results in a debilitating immune reaction in the gut to antigens in grain. The antigenic peptides recognized by the T cells that cause this disease are incompletely defined. Our understanding of the epitopes of pathogenic CD4(+ )T cells is based primarily on responses shown by intestinal T-cells in vitro to hydrolysates or polypeptides of gluten, the causative antigen. A protease-resistant 33-amino acid peptide from wheat alpha-gliadin is the immunodominant antigen, but little is known about the spectrum of T cell epitopes in rye and barley or the hierarchy of immunodominance and consistency of recognition of T-cell epitopes in vivo. We induced polyclonal gluten-specific T cells in the peripheral blood of celiac patients by feeding them cereal and performed a comprehensive, unbiased analysis of responses to all celiac toxic prolamins, a class of plant storage protein. The peptides that stimulated T cells were the same among patients who ate the same cereal, but were different after wheat, barley and rye ingestion. Unexpectedly, a sequence from omega-gliadin (wheat) and C-hordein (barley) but not alpha-gliadin was immunodominant regardless of the grain consumed. Furthermore, T cells specific for just three peptides accounted for the majority of gluten-specific T cells, and their recognition of gluten peptides was highly redundant. Our findings show that pathogenic T cells in celiac disease show limited diversity, and therefore suggest that peptide-based therapeutics for this disease and potentially other strongly HLA-restricted immune diseases should be possible. |
| spellingShingle | Tye-Din, J Stewart, J Dromey, J Beissbarth, T van Heel, D Tatham, A Henderson, K Mannering, S Gianfrani, C Jewell, D Hill, A McCluskey, J Rossjohn, J Anderson, R Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease. |
| title | Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease. |
| title_full | Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease. |
| title_fullStr | Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease. |
| title_full_unstemmed | Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease. |
| title_short | Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease. |
| title_sort | comprehensive quantitative mapping of t cell epitopes in gluten in celiac disease |
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