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

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

Salentijn et al. 2012

Celiac 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, the authors examined the variation of T-cell epitopes involved in CD in γ-gliadin transcripts of developing bread wheat grains.

A detailed analysis of the genetic variation present in γ-gliadin transcripts (a total of 69 different γ-gliadin sequences) 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. It was also shown that Transcripts from each locus differed in CD epitope content and composition. The Gli-D1 transcripts contained the highest frequency of authorized 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 26-mer γ-gliadin peptide that harbours four distinct CD epitopes is only present in D-genome γ-gliadins.

Taken together, the γ-gliadins from all three wheat genomes appear to be a significant source of CD epitopes. Like the α-gliadins, the highest number of potential immunogenic γ- gliadin peptides are encoded by the D genome of bread wheat which is thus the most critical genome regarding CD toxicity. However, gluten derived from tetraploid wheat varieties lacking the D genome is not tolerated by CD patients as well, indicating that the mere elimination of the D genome is not sufficient for the generation of safe wheat.

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