Publication Date:
2012-06-23
Description:
Background: Celiac disease (CD) is caused by an uncontrolled immune response to gluten, aheterogeneous 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; CDepitopes) that mediate the stimulation of HLA-DQ2/8 restricted T-cells. Next to thethoroughly characterized major T-cell epitopes derived from the alpha-gliadin fraction of gluten,gamma-gliadin peptides are also known to stimulate T-cells of celiac disease patients. To pinpointCD-toxic gamma-gliadins in hexaploid bread wheat, we examined the variation of T-cell epitopesinvolved in CD in gamma-gliadin transcripts of developing bread wheat grains. Results: A detailed analysis of the genetic variation present in gamma-gliadin transcripts of bread wheat (T.aestivum, allo-hexaploid, carrying the A, B and D genome), together with genomic gamma-gliadinsequences from ancestrally related diploid wheat species, enabled the assignment of sequencevariants to one of the three genomic gamma-gliadin loci, Gli-A1, Gli-B1 or Gli-D1. Almost half ofthe gamma-gliadin transcripts of bread wheat (49%) was assigned to locus Gli-D1. Transcripts fromeach locus differed in CD epitope content and composition. The Gli-D1 transcripts containedthe highest frequency of canonical CD epitope cores (on average 10.1 per transcript) followedby the Gli-A1 transcripts (8.6) and the Gli-B1 transcripts (5.4). The natural variants of themajor CD epitope from gamma-gliadins, DQ2-gamma-I, showed variation in their capacity to induce invitro proliferation of a DQ2-gamma-I specific and HLA-DQ2 restricted T-cell clone. Conclusions: Evaluating the CD epitopes derived from gamma-gliadins in their natural context of flankingprotein variation, genome specificity and transcript frequency is a significant step towardsaccurate quantification of the CD toxicity of bread wheat. This approach can be used topredict relative levels of CD toxicity of individual wheat cultivars directly from theirtranscripts (cDNAs).
Electronic ISSN:
1471-2164
Topics:
Biology
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