Gastroenterology

Gastroenterology

Volume 128, Issue 2, February 2005, Pages 393-401
Gastroenterology

Basic-alimentary tract
Mapping of gluten T-cell epitopes in the bread wheat ancestors: Implications for celiac disease

https://doi.org/10.1053/j.gastro.2004.11.003Get rights and content

Background & Aims: Celiac disease is a prevalent disorder characterized by a chronic intestinal inflammation driven by HLA-DQ2 or -DQ8-restricted T cells specific for ingested wheat gluten peptides. The dominant T-cell responses are to epitopes that cluster within a stable 33mer fragment formed by physiologic digestion of distinct α-gliadins. Celiac disease is treated by excluding all gluten proteins from the diet. Conceivably, a diet based on baking-quality gluten from a wheat species that expresses no or few T-cell stimulatory gluten peptides should be equally well tolerated by the celiac patients and, importantly, also be beneficial for disease prevention. Methods: To identify baking quality, harmless wheat, we followed the evolution of the wheat back to the species that most likely have contributed the AA, BB, and DD genomes to the bread wheat. Gluten were extracted from a large collection of these ancient wheat species and screened for T-cell stimulatory gluten peptides. Results: Distinct differences in the intestinal T-cell responses to the diploid species were identified. Interestingly, we found that the fragments identical or equivalent to the immunodominant 33mer fragment are encoded by α-gliadin genes on the wheat chromosome 6D and thus absent from gluten of diploid einkorn (AA) and even certain cultivars of the tetraploid (AABB) pasta wheat. Conclusions: These findings have implications for celiac disease because they raise the prospect of identifying or producing by breeding wheat species with low or absent levels of harmful gluten proteins.

Section snippets

Collection of the grain samples

Accessions of Triticum urartu (n = 40), Triticum monococcum (n = 15), Triticum tauschii (n = 9), Ae speltoides (n = 3), Triticum dicoccoides (n = 4), Triticum dicoccum (n = 3), and Triticum durum (n = 10) were collected. Some T urartu accessions had low grain numbers and were thus pooled. (Data on the individual accessions can be provided on request.)

Deletion mutants of the Chinese Spring bread wheat cultivar

Three ditelosomic lines that lack the short arm of chromosomes 6A (Dt 6 AL), 6B (Dt 6 BL), and 6D (Dt 6 DL) and 5 deletion mutants (6AS-1, 6BS-1,

Screening the AA, BB, and DD genome wheat species with intestinal T-cell clones

Gluten from selected samples of the AA donor (T urartu No. 2), the potential BB donor (Ae speltoideus No. 1), and the DD donor (T tauschii No. 1) were treated with TG2 and tested for recognition by 14 different celiac lesion-derived T-cell clones specific for 3 α-gliadin epitopes and 5 γ-gliadin epitopes (Table 1 and Figure 2, upper panel).

The DD genome donor expresses all the gluten T-cell epitopes

The gluten digests of all the nine T tauschii accessions were efficiently recognized by all the α- and γ-gliadin specific T-cell clones (data not shown),

Discussion

Here, we describe how insights into the evolution of the modern bread wheat can be combined with knowledge on celiac disease pathogenesis in an integrated approach to identify wheat strains that are devoid of or have low contents of T-cell stimulatory gluten sequences. We have extracted the gluten fraction from selected samples of the diploid wheat species that are the origin of the bread wheat and tested for recognition by a panel of celiac lesion-derived, gluten-specific T cells. Our main

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    Supported by research grants from the Research Council of Norway (132864/300), the European Commission (BMH4-CT98-3087, QLKT-2000-00657), and the Norwegian Foundation for Health and Rehabilitation.

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