tissue transglutaminase
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A repair enzyme the immune system turns against — it modifies gluten into a more dangerous form, then becomes a target itself.
Tissue transglutaminase (tTG, also called TG2) is an enzyme found throughout the body — in the gut, liver, bone, brain, and heart. Its normal function is tissue repair: it cross-links proteins to stabilise and reinforce damaged tissue. In celiac disease, it inadvertently makes gluten far more immunogenic, and then becomes the direct target of an autoimmune attack.
What tTG Does to Gluten
When gliadin peptides cross the epithelial barrier into the intestinal tissue, they encounter tTG. The enzyme modifies them in two ways:
1. Deamidation tTG converts glutamine residues in gliadin to glutamate — a simple chemical change that adds a negative charge to the peptide. This small change dramatically increases how tightly the peptide binds to HLA-DQ2/DQ8 molecules on antigen-presenting cells. Tighter binding = longer presentation = stronger T cell response.
2. Transamidation tTG can cross-link gliadin peptides directly to itself, forming a covalent complex. This creates entirely new molecular shapes (neoepitopes) that the immune system has never encountered before — and reacts to aggressively. The resulting antibodies target tTG itself, not just gliadin.
tTG as Autoimmune Target
The anti-tTG antibody response is what makes celiac an autoimmune disease rather than just an allergic one. The immune system starts attacking tTG wherever it is expressed — including the gut lining, liver, bone, and nervous system. This is a major reason for the wide range of extraintestinal manifestations.
Clinical Significance
Anti-tTG IgA is the primary diagnostic target — the ttg-iga-test measures antibodies to tTG in blood. High levels indicate active immune response to gluten. Levels fall on a gluten-free-diet as gluten exposure (and thus tTG modification of gliadin) decreases.
tTG is also a target of emerging therapies — some research approaches aim to block tTG activity to prevent gluten peptide modification before it triggers the immune cascade.
Related Concepts
gliadin | deamidation | hla-dq2-dq8 | ttg-iga-test | autoantibodies-celiac | tight-junctions | cd4-t-cells