The 33-mer gliadin peptide forms thin plate type superstructures that activae TLRs

DODERO, V.I.; HERRERA, M.G; PIZZUTO, M.; LONEZ, C; SEWALD, N.; RUYSSCHAERT , J-M

Congreso; 19 th International Union for pure and applied Biophysics Congress; 2017

Gliadin is one of the storages protein in wheat. It is known that gliadin is not fulled degraded by humans and after the normal gastric and pancreatic digestion some rather larg peptidic fragments remains unprocesed. the most immunogenic is the 33.-mer gliadin peptide, wichh is found in human fecesand urine, proving not only its proteolytic resistancein vivo but more importantly its transport through the entire human system. The central role of 33-mer in the adaptative system is well described in th case of celiac disease, although the mechamism responsible of the onset of the innate immune respone is unkown. Previously, we showed that 33-mer oligomerize in a cocnnetraion dependent manner . Here, we report that thin plate planar structures of 33-mer actuvate nuclear factor kappa beta via a specific Toll-like receptor 2 and 4 dependet pathway and induce thesecreation of proimflamatory cytokines such as IP-10 and TNF-alfa. These properties of 33-mer aggregates support the existing hypothesis of baterial mimicry behavoir of gliadin peptides in the activation of innate immunological responses, opening a new era in the understanding of gluten related disorders.