Celiac Immunogenic Potential of α-Gliadin Epitope Variants from Triticum and Aegilops Species

Abstract

This study investigates the immunotoxic potential of α-gliadins in wheat species and their implications for celiac disease (CD). Gluten, the primary structural protein complex in wheat, contains α-gliadins, which are rich in T-cell stimulating epitopes (DQ2.5-glia-α1, DQ2.5-glia-α2, and DQ2.5-glia-α3) that trigger immune responses in individuals with CD. The analysis spanned diploid, tetraploid, and hexaploid wheat species, focusing on the abundance and immunostimulatory capacity of canonical epitopes and their variants.The findings reveal that DQ2.5-glia-α1 and DQ2.5-glia-α3 are more prevalent than DQ2.5-glia-α2. Canonical DQ2.5-glia-α1 is notably abundant in genomes of the BBAADD, AA, and DD types, while DQ2.5-glia-α3 epitope variants are highly represented in BBAADD and BBAA wheats, despite a lower presence of the canonical form. Importantly, the introduction of a natural amino acid substitution (Q to H) at any position effectively neutralized the immunotoxicity of the epitopes without compromising wheat's functional properties.This work underscores the potential of targeted amino acid substitutions as a strategy to develop wheat varieties that are safer for individuals with CD while preserving their technological value.