deamidation
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A small chemical change that turns a mildly irritating peptide into a powerful immune trigger.
Deamidation is one of two chemical modifications that tissue-transglutaminase (tTG) performs on gliadin peptides once they cross the intestinal barrier. It converts glutamine residues within gliadin to glutamate — removing an amino group (-NH₂) and replacing it with a hydroxyl (-OH), which creates a negative charge on the peptide.
Why a Negative Charge Matters
This is not intuitive at first — a tiny chemical change causing an autoimmune disease. The reason it matters is geometry and binding:
HLA-DQ2 and HLA-DQ8 molecules have a peptide-binding groove with positively charged "pockets." Deamidated gluten peptides, now carrying negative charges at specific positions, fit into these pockets with dramatically higher affinity — up to ~100× tighter than unmodified peptides. A tighter, more stable HLA–peptide complex persists longer on the surface of antigen-presenting cells, giving cd4-t-cells more time to see it and a stronger signal to respond.
Without deamidation, gluten peptides would be weak HLA binders — not enough signal to reliably trigger a full immune response. Deamidation is what converts dietary exposure into disease.
Deamidation vs Transamidation
tTG performs two distinct modifications on gliadin:
| Modification | What Happens | Consequence |
|---|---|---|
| Deamidation | Glutamine → glutamate (charge change) | Stronger HLA binding → T cell activation |
| Transamidation | Gliadin cross-linked to tTG itself | New neoepitopes → anti-tTG antibodies (autoimmunity) |
Both contribute to celiac pathogenesis but through different arms: deamidation drives the T cell response, transamidation drives the B cell/autoantibody response.
Diagnostic Relevance
The TTG IgA test detects antibodies against tTG itself (produced through transamidation). A separate test — deamidated gliadin peptide IgG (DGP IgG) — directly detects antibodies against deamidated gliadin. DGP IgG is used when IgA deficiency makes TTG IgA testing unreliable.
Related Concepts
tissue-transglutaminase | gliadin | hla-dq2-dq8 | cd4-t-cells | autoantibodies-celiac | ttg-iga-test