Clinical–alimentary tractNatural Variation in Toxicity of Wheat: Potential for Selection of Nontoxic Varieties for Celiac Disease Patients
Section snippets
Database Searches
A wheat gliadin and glutenin subset was extracted from the Uniprot database using the SRS program (www.ebi.ac.uk). All epitope sequences listed in Table 1 were searched for full similarity against this subset using the stand-alone Macintosh (Apple, Cupertino, CA) version of the program PeptideSearch (http://www.mann.embl-heidelberg.de/GroupPages/PageLink/peptidesearchpage.html).
Description of the Different Wheat Accessions
The wheat accessions used in this study were obtained from the small-grain cereal collection maintained by the Centre
Matching of Gliadin- and Glutenin-Derived T-Cell Epitopes With Gluten Proteins
It is unknown if all gluten genes are equally toxic for CD patients. The sequences of hundreds of gluten proteins are available through databases. We have aligned the sequence of 11 T-cell–stimulatory sequences from α-gliadin, γ-gliadin, LMW-glutenin, and HMW-glutenin with the gliadin and glutenin proteins present in the Uniprot database (Table 1). Strikingly, although all γ-gliadins contained 1 or more T-cell–stimulatory sequences, the large majority of the LMW-glutenin and one third of the
Discussion
CD is the most common food intolerance in the Western hemisphere: approximately .5% to 1% of the population is now known to have the disease, although the symptoms vary widely among patients. Classic symptoms include diarrhea, stomachache, and failure to thrive. These are the result of a lesion in the small intestine characterized by villous atrophy. T cells isolated from small intestinal biopsy specimens of patients have been shown to respond specifically to gluten-derived peptides bound to
References (31)
- et al.
Gliadin T cell epitope selection by tissue transglutaminase in celiac disease
J Biol Chem
(2002) - et al.
Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease
Gastroenterology
(1998) - et al.
HLA-DQ2-restricted T-cell recognition of gluten-derived peptides in celiac disease. Influence of amino acid substitutions in the membrane distal domain of DQ beta 1*0201
Hum Immunol
(1995) - et al.
The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides
Gastroenterology
(2002) - et al.
Intestinal T-cell responses to high-molecular-weight glutenins in celiac disease
Gastroenterology
(2003) - et al.
Characterization of cereal toxicity for celiac disease patients based on protein homology in grains
Gastroenterology
(2003) - et al.
Mapping of gluten T-cell epitopes in bread wheat ancestorsimplications for celiac disease
Gastroenterology
(2005) - et al.
In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope
Nat Med
(2000) - et al.
Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease
Nat Med
(1998) - et al.
T cells from celiac disease lesions recognize gliadin epitopes deamidated in situ by endogenous tissue transglutaminase
Eur J Immunol
(2001)
HLA binding and T cell recognition of a tissue transglutaminase-modified gliadin epitope
Eur J Immunol
Identification of a gliadin T-cell epitope in coeliac diseasegeneral importance of gliadin deamidation for intestinal T-cell recognition
Scand J Immunol
Specificity of tissue transglutaminase explains cereal toxicity in celiac disease
J Exp Med
Selective deamidation by tissue transglutaminase strongly enhances gliadin-specific T cell reactivity
J Immunol
Gliadin-specific, HLA-DQ (alpha 1*0501, beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients
J Exp Med
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Supported by the Celiac Disease Consortium, an Innovative Cluster approved by the Netherlands Genomics Initiative and partially funded by the Dutch Government (BSIK03009), the Stimuleringsfonds Voedingsonderzoek Leiden University Medical Center, by grants from the European Community (QLRT-2000-00657 and QLRT-2002-02077), and by the Center for Medical Systems Biology, a center of excellence approved by the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research.