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The main villain in wheat — the prolamin fraction that drives the celiac immune response.

Gliadin is one of the two major protein fractions in wheat gluten (the other being glutenin). It belongs to the prolamins family — storage proteins rich in proline and glutamine. Gliadin is the fraction most responsible for triggering celiac disease because it contains the specific peptide sequences that resist digestion, cross the gut barrier, and provoke the strongest immune responses.

Structure: Why It Survives Digestion

Gliadin is roughly 30–80% proline and glutamine by amino acid content. Proline creates rigid "kinks" in the peptide chain that block the active sites of gut proteases (the enzymes that normally chop proteins into harmless fragments). The result: large gliadin peptide fragments survive the full length of the digestive process and arrive at the small intestinal lining intact.

The Key Peptides

Two gliadin-derived peptide fragments are especially well-characterised:

Alpha-2 gliadin 33-mer (33 amino acids)

  • The most immunogenic gliadin fragment known
  • Completely resistant to all digestive enzymes (gastric, pancreatic, and brush-border)
  • Contains 6 overlapping T cell epitopes — multiple T cells can respond to it simultaneously
  • Potently activates both the adaptive and (via IL-15) innate immune responses

Alpha-2 gliadin p31–43 / p31–49

Modification by tTG

When gliadin peptides cross the epithelial barrier, tissue-transglutaminase deamidates them — converting specific glutamine residues to glutamate. This small chemical change increases their binding affinity to hla-dq2-dq8 by ~100-fold, turning moderately immunogenic peptides into potent triggers.

Wheat Varieties and Gliadin Content

All wheat subspecies contain gliadin: spelt, durum, khorasan, and hybrids like triticale. Selective breeding and genetic engineering to reduce alpha-gliadin epitope content is an active research direction (see modified wheat).

prolamins | tissue-transglutaminase | deamidation | hla-dq2-dq8 | tight-junctions | cd4-t-cells | il-15 | glutenases

Referenced In

mechanism | causes | glossary | research_plan