Wheat gluten proteins: from taxonomy to toxic epitopes

Wheat is one of the most widely consumed cereals worldwide. However, wheat-based foods have to be strictly avoided by a substantial number of people suffering from celiac disease (CD), a gluten intolerance (approximately 1% of the general population). Gluten, the main seed storage protein, contains hundreds of highly homologous proteins characterized by high contents of glutamine and proline. This peculiar aminoacidic composition strongly hampered the physiologic digestion by gastrointestinal proteases, and large peptides with immunogenic potential are delivered in the gut, eliciting gut mucosa inflammation in CD patients. By using in vitro and in vivo assays, based on intestinal T cells and peripheral blood cells from CD patients after a brief gluten oral challenge, more than 50 different gluten peptides have been identified so far that elicit an inflammatory T-cell response in celiac. The comprehensive definition of the gluten epitope repertoire is crucial for designing immunological or enzymatic therapies as alternatives to the gluten-exclusion diet, as well as for obtaining wheat species naturally devoid of the immunogenic sequences, or resulting from gene silencing molecular engineering. Furthermore, the availability of wheat species with low immunotoxic gluten proteins, although not suitable for the diet of celiacs, could have important implications for disease prevention in genetically risky subjects.