In search of tetraploid wheat accessions reduced in celiac disease-related gluten epitopes

Broeck, Hetty van den; Chen, Hongbing; Lacaze, Xavier; Dusautoir, Jean-Claude; Gilissen, L.J.W.J.; Smulders, M.J.M.; Meer, Ingrid van der

doi:10.1039/c0mb00046a

Cited by 55 publications

(30 citation statements)

References 47 publications

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“…Although durum wheat contains only the A and B genome, six protein fragments with a D-genomic signature were found. Four of these came from a genebank accession of a landrace (CGN08360, ‘Diha Dzhavakhetskaja’) that is known to consist of a mixture of tetraploid and hexaploid genotypes with indistinguishable phenotypes [35]. Such a mixture is not uncommon in genebank accessions [35,36].…”

Section: Resultsmentioning

confidence: 99%

“…Four of these came from a genebank accession of a landrace (CGN08360, ‘Diha Dzhavakhetskaja’) that is known to consist of a mixture of tetraploid and hexaploid genotypes with indistinguishable phenotypes [35]. Such a mixture is not uncommon in genebank accessions [35,36]. The two other alpha-gliadin protein fragments with a D genome signature showed also signatures of the B genome alpha-gliadins and were present at low abundance in several breeding lines of durum wheat (normalised transcript abundance 0.20 to 0.13).…”

Section: Resultsmentioning

confidence: 99%

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Quantitative and qualitative differences in celiac disease epitopes among durum wheat varieties identified through deep RNA-amplicon sequencing

Salentijn¹,

Esselink²,

Goryunova

et al. 2013

BMC Genomics

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BackgroundWheat gluten is important for the industrial quality of bread wheat (Triticum aestivum L.) and durum wheat (T. turgidum L.). Gluten proteins are also the source of immunogenic peptides that can trigger a T cell reaction in celiac disease (CD) patients, leading to inflammatory responses in the small intestine. Various peptides with three major T cell epitopes involved in CD are derived from alpha-gliadin fraction of gluten. Alpha-gliadins are encoded by a large multigene family and amino acid variation in the CD epitopes is known to influence the immunogenicity of individual gene family members. Current commercial methods of gluten detection are unable to distinguish between immunogenic and non-immunogenic CD epitope variants and thus to accurately quantify the overall CD epitope load of a given wheat variety. Such quantification is indispensable for correct selection of wheat varieties with low potential to cause CD.ResultsA 454 RNA-amplicon sequencing method was developed for alpha-gliadin transcripts encompassing the three major CD epitopes and their variants. The method was used to screen developing grains on plants of 61 different durum wheat cultivars and accessions. A dedicated sequence analysis pipeline returned a total of 304 unique alpha-gliadin transcripts, corresponding to a total of 171 ‘unique deduced protein fragments’ of alpha-gliadins. The numbers of these fragments obtained in each plant were used to calculate quantitative and quantitative differences between the CD epitopes expressed in the endosperm of these wheat plants. A few plants showed a lower fraction of CD epitope-encoding alpha-gliadin transcripts, but none were free of CD epitopes.ConclusionsThe dedicated 454 RNA-amplicon sequencing method enables 1) the grouping of wheat plants according to the genetic variation in alpha-gliadin transcripts, and 2) the screening for plants which are potentially less CD-immunogenic. The resulting alpha-gliadin sequence database will be useful as a reference in proteomics analysis regarding the immunogenic potential of mature wheat grains.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Quantitative and qualitative differences in celiac disease epitopes among durum wheat varieties identified through deep RNA-amplicon sequencing

Salentijn¹,

Esselink²,

Goryunova

et al. 2013

BMC Genomics

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“…DQ2-α-I, DQ2-α-II; [46] and/or DQ2-γ-I, this study). Such varieties would help to reduce the presence of immunogenic CD epitopes in wheat flour and, while not safe for consumption by patients, might help to prevent the onset of CD in people that carry genetic risk factors [44,45]. However, introgression from the diploid to the hexaploid level is a time-consuming process, and consequently it will take many years before the product of such a synthetic hexaploidisation has been bred to sufficient agronomic quality.…”

Section: Discussionmentioning

confidence: 99%

“…This diversity is qualitatively reflected at the protein level [42], but not all genes are expressed evenly. Epitope content of the genes varies [39], just as it varied among α-gliadins [31,43-45] according to the genome of origin of the loci.…”

Section: Introductionmentioning

confidence: 99%

Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation

Salentijn¹,

Mitea

Goryunova

et al. 2012

BMC Genomics

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BackgroundCeliac disease (CD) is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins. The CD-toxicity of these proteins and their derived peptides is depending on the presence of specific T-cell epitopes (9-mer peptides; CD epitopes) that mediate the stimulation of HLA-DQ2/8 restricted T-cells. Next to the thoroughly characterized major T-cell epitopes derived from the α-gliadin fraction of gluten, γ-gliadin peptides are also known to stimulate T-cells of celiac disease patients. To pinpoint CD-toxic γ-gliadins in hexaploid bread wheat, we examined the variation of T-cell epitopes involved in CD in γ-gliadin transcripts of developing bread wheat grains.ResultsA detailed analysis of the genetic variation present in γ-gliadin transcripts of bread wheat (T. aestivum, allo-hexaploid, carrying the A, B and D genome), together with genomic γ-gliadin sequences from ancestrally related diploid wheat species, enabled the assignment of sequence variants to one of the three genomic γ-gliadin loci, Gli-A1, Gli-B1 or Gli-D1. Almost half of the γ-gliadin transcripts of bread wheat (49%) was assigned to locus Gli-D1. Transcripts from each locus differed in CD epitope content and composition. The Gli-D1 transcripts contained the highest frequency of canonical CD epitope cores (on average 10.1 per transcript) followed by the Gli-A1 transcripts (8.6) and the Gli-B1 transcripts (5.4). The natural variants of the major CD epitope from γ-gliadins, DQ2-γ-I, showed variation in their capacity to induce in vitro proliferation of a DQ2-γ-I specific and HLA-DQ2 restricted T-cell clone.ConclusionsEvaluating the CD epitopes derived from γ-gliadins in their natural context of flanking protein variation, genome specificity and transcript frequency is a significant step towards accurate quantification of the CD toxicity of bread wheat. This approach can be used to predict relative levels of CD toxicity of individual wheat cultivars directly from their transcripts (cDNAs).

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“…However, not all wheat sources are genetically identical. There is a heterogeneity in the content of storage proteins for different wheat cultivars [21,25] and landraces [26]. In fact, the level of the celiac-related Glia-a9 epitope was much higher in modern wheat varieties than in the ancient landraces [21,25].…”

Section: Introductionmentioning

confidence: 99%

The Impact of Diet Wheat Source on the Onset of Type 1 Diabetes Mellitus—Lessons Learned from the Non-Obese Diabetic (NOD) Mouse Model

Gorelick¹,

Yarmolinsky²,

Budovsky³

et al. 2017

Nutrients

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Nutrition, especially wheat consumption, is a major factor involved in the onset of type 1 diabetes (T1D) and other autoimmune diseases such as celiac. While modern wheat cultivars possess similar gliadin proteins associated with the onset of celiac disease and T1D, alternative dietary wheat sources from Israeli landraces and native ancestral species may be lacking the epitopes linked with T1D, potentially reducing the incidence of T1D. The Non-Obese Diabetic (NOD) mouse model was used to monitor the effects of dietary wheat sources on the onset and development of T1D. The effects of modern wheat flour were compared with those from either T. aestivum, T. turgidum spp. dicoccoides, or T. turgidum spp. dicoccum landraces or a non-wheat diet. Animals which received wheat from local landraces or ancestral species such as emmer displayed a lower incidence of T1D and related complications compared to animals fed a modern wheat variety. This study is the first report of the diabetogenic properties of various dietary wheat sources and suggests that alternative dietary wheat sources may lack T1D linked epitopes, thus reducing the incidence of T1D.

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In search of tetraploid wheat accessions reduced in celiac disease-related gluten epitopes

Cited by 55 publications

References 47 publications

Quantitative and qualitative differences in celiac disease epitopes among durum wheat varieties identified through deep RNA-amplicon sequencing

Quantitative and qualitative differences in celiac disease epitopes among durum wheat varieties identified through deep RNA-amplicon sequencing

Celiac disease T-cell epitopes from gamma-gliadins: immunoreactivity depends on the genome of origin, transcript frequency, and flanking protein variation

The Impact of Diet Wheat Source on the Onset of Type 1 Diabetes Mellitus—Lessons Learned from the Non-Obese Diabetic (NOD) Mouse Model

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