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| Article Authors: | Willemijn Vader; Yvonne Kooy; Peter Van Veelen; Arnoud De Ru; Diana Harris; Willemien Benckhuijsen; Salvador Peña; Luisa Mearin; Jan Wouter Drijfhout; Frits Koning |
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| Article Title: | The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides. |
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| Reference ID: | 1005489 |
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| Abstract: | BACKGROUND & AIMS: Gluten (GLU)-specific T-cell responses in HLA-DQ2 positive adult celiac disease (CD) patients are directed to an immunodominant alpha-gliadin (GLIA) peptide that requires deamidation for T-cell recognition. The aim of the current study was to determine which GLU peptide(s) are involved early in disease. METHODS: We have characterized the GLU-specific T-cell response in HLA-DQ2 positive children with recent onset CD. RESULTS: We found that 50% of these patients do not respond to the alpha-GLIA peptide but to a diverse set of GLIA and glutenin (GLT) peptides, including 6 novel epitopes. Moreover, individual patients respond to distinct (combinations of) GLU peptides. T-cell cross-reactivity toward homologous GLIA and GLT peptides was observed, which might play a role in the initial spreading of the GLU-specific T-cell response. Although all pediatric patients displayed deamidation-dependent responses, deamidation-independent responses were found in the majority of patients as well. Finally, T-cell responses to 3 of these novel GLU peptides were found in adult CD patients. CONCLUSIONS: The diversity of the GLU-specific T-cell response is far greater than was previously appreciated. Both adult and young CD patients can respond to a diverse repertoire of GLU peptides. The observation that T-cell responses to 3 of the novel peptides are independent of deamidation indicates that T-cell responses can be initiated toward native GLU peptides. The possibility that deamidation drives the GLU response toward immunodominant T-cell stimulatory peptides after disease initiation is discussed. |
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| Affiliations: | Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands. |
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| Date: | 2002 |
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| Reference Type: | Literature |
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| PubMed ID: | 12055577 |
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| Journal: | Gastroenterology |
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| Journal Volume: | 122 |
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| Article Pages: | 1729-37 |
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| Journal ISSN: | 0016-5085 |
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| Article Chemical List: | Epitopes;HLA-DQ Antigens;HLA-DQ2 antigen, human;Peptide Fragments;Glutens;Gliadin;glutenin |
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| Article MeSH List: | Amino Acid Sequence; Celiac Disease(immunology); Cell Line; Child; Child, Preschool; Epitopes; Gliadin(immunology); Glutens(analogs & derivatives; genetics; immunology); HLA-DQ Antigens(analysis); Humans; Infant; Peptide Fragments(genetics; immunology); T-Lymphocytes(immunology) |
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| Curation Last Updated: | 2013-05-28 20:53:25 |
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