Abstract | BACKGROUND & AIMS: Developing antigen-specific approaches for diagnosis and treatment of celiac disease requires a detailed understanding of the specificity of T cells for gluten. The existing paradigm is that T-cell lines and clones from children differ from those of adults in the hierarchy and diversity of peptide recognition. We aimed to characterize the T-cell response to gluten in children vs adults with celiac disease. METHODS: Forty-one children with biopsy-proven celiac disease (median age, 9 years old; 17 male), who had been on strict gluten-free diets for at least 3 months, were given a 3-day challenge with wheat; blood samples were collected and gluten-specific T cells were measured. We analyzed responses of T cells from these children and from 4 adults with celiac disease to a peptide library and measured T-cell receptor bias. We isolated T-cell clones that recognized dominant peptides and assessed whether gluten peptide recognition was similar between T-cell clones from children and adults. RESULTS: We detected gluten-specific responses by T cells from 30 of the children with celiac disease (73%). T cells from the children recognized the same peptides that were immunogenic to adults with celiac disease; deamidation of peptides increased these responses. Age and time since diagnosis did not affect the magnitude of T-cell responses to dominant peptides. T-cell clones specific for dominant α- or ω- gliadin peptides from children with celiac disease had comparable levels of reactivity to wheat, rye, and barley peptides as T-cell clones from adults with celiac disease. The α- gliadin-specific T cells from children had biases in T-cell receptor usage similar to those in adults. CONCLUSIONS:
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Authors | Melinda Y Hardy, Adam Girardin, Catherine Pizzey, Donald J Cameron, Katherine A Watson, Stefania Picascia, Renata Auricchio, Luigi Greco, Carmen Gianfrani, Nicole L La Gruta, Robert P Anderson, Jason A Tye-Din |
Journal | Gastroenterology
(Gastroenterology)
Vol. 149
Issue 6
Pg. 1541-1552.e2
(Nov 2015)
ISSN: 1528-0012 [Electronic] United States |
PMID | 26226573
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Peptides
- Receptors, Antigen, T-Cell
- Glutens
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Topics |
- Adult
- Age Factors
- Aging
(immunology)
- Celiac Disease
(diagnosis, immunology)
- Child
- Clone Cells
(immunology)
- Diet, Gluten-Free
- Female
- Glutens
(immunology)
- Humans
- Male
- Peptides
(immunology)
- Receptors, Antigen, T-Cell
(immunology)
- T-Lymphocytes
(immunology)
- Time Factors
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