Variations in immunodominant epitope and molecular conformation of alpha-gliadins in elite Ethiopian durum wheat cultivars

Abstract Alpha-gliadins are the predominant immunogenic fractions of gluten proteins with strong T cell stimulatory epitopes that affect celiac disease (CD) patients. To obtain essential information on the CD epitopes of Ethiopian durum wheat, molecular characterizations were conducted using α-gliad...
Ausführliche Beschreibung

Abstract Alpha-gliadins are the predominant immunogenic fractions of gluten proteins with strong T cell stimulatory epitopes that affect celiac disease (CD) patients. To obtain essential information on the CD epitopes of Ethiopian durum wheat, molecular characterizations were conducted using α-gliadin gene clones of three elite Ethiopian durum wheat cultivars. Deduced amino acid sequences of the three selected clones share all the known primary features of α-gliadins and core sequences of CD epitopes. Several insertions and deletions (InDels), and substitutions in the core and adjacent sequences of the epitopes are dissimilar among the deduced α-gliadins. Due mainly to these sequence variations, the core sequences of all the toxic epitopes are in one to four mismatches to their canonical sequences, showing distinct patterns among the deduced α-gliadins, except one canonical epitope from cv. Assasa. These sequence variations also result in a drastic difference in peptide cleavage patterns by proteases contained in human gastric and duodenal juices. In addition, characteristic differences in disulfide connectivity, and hydropathy and polarity of amino acid residues correlate well with noticeable variations in conformational ensembles of the peptides, especially at the region harboring multiple CD epitopes at the N-terminal region. α-Gliadin from cv. Assasa is unique in that it has mostly variant toxic epitopes and all the epitope motifs are cleaved by multiple enzymes at up to five positions. Ethiopian germplasms expressing α-gliadins with divergent sequences at the epitope motifs together with higher susceptibility to proteases in human digestive systems could be potential resources for the development of hypoallergenic cultivars. Ausführliche Beschreibung