Subtractive immunogenicity of super-deamidated wheat gluten: targeting the attenuation of immune-recognition of tissue transglutaminase–peptide complexes

Super-deamidation can eliminate acyl donor sites in wheat gluten to subtract immunogenicity of celiac disease (CD) by blocking endogenous tTG-mediated deamidation of gluten. However, its efficacy and related mechanisms in reducing immunogenicity through modulation of tTG-peptide complexes remains unclear. In this study, the digestive stability and tTG-peptide complexes immunogenicity of super-deamidated wheat gluten (SDWG) were evaluated to clarify the above mechanisms in suppressed tTG-peptide complexes immune responses. SDWG showed a 23.41% increase in the degree of hydrolysis and a 1.44 mg/mL increase in peptide concentration, potentially reducing to ~66% in CD related immunogenic epitopes compared with those of nature wheat gluten (NWG). Digested SDWG peptides (150–2,400 μg/mL) decreased intracellular ROS, lowered cell permeability, increased TEER value, and enhanced Occludin expression compare to NWG. Moreover, SDWG reduced the binding capacity between digested peptides and tTG, decreased interfacial adsorbed mass by 25.64 ng/cm² and the enthalpy change (ΔH) by 1.6 kcal/mol as well as the immunogenicity potential of the complexes. These results indicate that SDWG could improve digestibility and attenuate tTG-peptide immune-recognition, thereby reducing immunogenicity. This research highlights the SDWG potential for applications in low-immunogenic gluten-based food ingredients.