Docking of peptide candidates to HLA-DQ2 and HLA-DQ8 basket as a tool for predicting potential immunotoxic peptides toward celiac diseased people

Cereal food products susceptible to generate immunotoxic peptides play a key role in the epidemiology of celiac disease and associated non IgE-mediated gluten intolerance disorders. The specific recognition by the basket of the HLA-DQ2 and HLA-DQ2 serotype groups of the corresponding immunotoxic peptides, triggers a cascade of molecular recognition events that lead to the inflammatory mechanisms responsible for the erosion of the villi covering the intestinal mucosa, currently observed in the severe forms of celiac disease. Accordingly, different in silico approaches have been proposed to predict the possible occurrence of immunotoxic peptides or immunotoxic-like peptides in food proteins of plant origin and, especially, of edible cereals, to prevent the consumption of deleterious food products by celiac disease suffering people. Among these approaches, the docking of putative imunotoxic-like peptides to the HLA-DQ2 and HLA-DQ8 basket consists of an interesting tool, especially when coupled to the bioinformatic research for amino acid sequence identities with genuine immunotoxic peptides from the gliadin and glutenin proteins already identified in gluten-containing cereals. However, the specificity of the DQ2- and DQ8-peptides has to be checked since some promiscuity has been observed among the immunotoxic peptides concerning their HLA-DQ2/HLA-DQ8-binding specificity. Docking experiments performed with a series of 26 genuine immunotoxic peptides from gluten-containing cereals (wheat, oat, barley, rye) were compared to the glutamine/proline-containing peptides from the non-gluten corn and rice cereals, for their HLA-DQ2/HLA-DQ8-binding capacity. None of the peptides from non-gluten cereals was able to completely bind the HLA-DQ2/HLA-DQ8 basket whereas all of the 26 genuine immunotoxic peptides from the gluten-containing cereals become adequately bound to the HLA-DQ basket, even though some promiscuity occurred between the DQ2- and DQ8-specific peptides. Docking to the HLA-DQ2/HLA-DQ8 serotypes thus consists of a relevant tool to predict the immunotoxic propensity of food proteins toward celiac disease suffering people, provided their sequence are known. Les céréales dont la protéolyse digestive est susceptible de générer des peptides immunotoxiques jouent un rôle déterminant dans l’épidémiologie de la maladie cœliaque et des intolérances sévères au gluten non IgE-médiées. La reconnaissance spécifique des peptides immunotoxiques par la corbeille des sérotype