Consistency in Polyclonal T-cell Responses to Gluten between Children and Adults with Celiac Disease

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

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Abstract

Background and 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 T cells from children with celiac disease recognize similar gluten peptides as T cells from adults with celiac disease. The findings indicate that peptide-based diagnostics and therapeutics for adults may also be used for children.

Original languageEnglish
Pages (from-to)1541-1552
Number of pages12
JournalGastroenterology
Volume149
Issue number6
DOIs
Publication statusPublished - 1 Nov 2015
Externally publishedYes

Keywords

  • Food Intolerance Mechanisms
  • Immune Response
  • Immunity
  • Pediatric
  • T-Cell Epitope

Cite this

Hardy, M. Y., Girardin, A., Pizzey, C., Cameron, D. J., Watson, K. A., Picascia, S., Auricchio, R., Greco, L., Gianfrani, C., La Gruta, N. L., Anderson, R. P., & Tye-Din, J. A. (2015). Consistency in Polyclonal T-cell Responses to Gluten between Children and Adults with Celiac Disease. Gastroenterology, 149(6), 1541-1552. https://doi.org/10.1053/j.gastro.2015.07.013