Gluten antibodies: the pathway in the body

This page shows the biochemical pathway behind the laboratory value Anti-TG2 and anti-gliadin: which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

Gluten is a mixture of storage proteins from wheat, rye and barley. Some of its fragments are modified by transglutaminase 2 and can start an immune response with antibodies against gliadin and against this enzyme.

The pathway step by step

1. Gluten in food → Long fragments Digestive enzymes Stomach and gut enzymes break most proteins down to single amino acids. At proline-rich sites they do not cut, so longer fragments remain. Source 1
2. Long fragments → 33-mer peptide A fragment of 33 amino acids survives digestion almost unchanged. It is the best studied of these peptides. Source 1
3. 33-mer peptide → Passage into tissue A small share of these fragments passes through or between the gut cells into the lining beneath. Source 2
4. Fragment in the tissue → Modified peptide Transglutaminase 2 · Calcium The enzyme converts individual glutamine units into glutamic acid. This process is called deamidation; afterwards the fragment carries negative charges. Source 3
5. Modified peptide → Binding to HLA-DQ2/DQ8 · HLA-DQ2, HLA-DQ8 Immune cells display fragments on HLA molecules. Negatively charged fragments fit especially well into the binding groove of DQ2 and DQ8. Source 2
6. Binding to HLA-DQ2/DQ8 → T cells recognise it Certain T cells recognise exactly this combination of HLA molecule and modified fragment. As a result they become active and divide. Source 2
7. T cells recognise it → B cells are activated The T cells pass signals on to B cells. B cells that recognise the fragment itself become active, as do those that recognise the enzyme next to it. Source 3, 4
8. B cells are activated → Antibodies in the blood The B cells produce antibodies: against gliadin (AGA) and against the body's own transglutaminase 2 (anti-TG2). Both can be measured in the blood. Source 3, 4

Cofactors in this pathway

• Calcium — Activates transglutaminase 2, which deamidates glutamine in gluten fragments Source 3In the ORY catalogue as a laboratory value: Calcium (intrazellulär)
• Glutamine — Frequent building block of gluten and the site of deamidation Source 1, 3In the ORY catalogue as a laboratory value: Glutamin
• Glutamate (glutamic acid) — Formed from glutamine by deamidation and carries the negative charge Source 3In the ORY catalogue as a laboratory value: Glutamat
• Proline — Frequent building block of gluten; digestive enzymes do not cut at proline-rich sites Source 1

Sources

1. Shan L, Molberg O, Parrot I et al. Structural basis for gluten intolerance in celiac sprue. Science 2002 · PubMed 12351792
2. Sollid LM, Jabri B. Triggers and drivers of autoimmunity: lessons from coeliac disease. Nat Rev Immunol 2013 · PubMed 23493116
3. Rauhavirta T, Hietikko M, Salmi T et al. Transglutaminase 2 and Transglutaminase 2 Autoantibodies in Celiac Disease: a Review. Clin Rev Allergy Immunol 2019 · PubMed 27263022
4. Lindfors K, Ciacci C, Kurppa K et al. Coeliac disease. Nat Rev Dis Primers 2019 · PubMed 30631077

Related pathways

• Magnesium — Calcium (intrazellulär), Glutamat

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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