IDENTIFICATION OF A GLIADIN T-CELL EPITOPE IN CELIAC-DISEASE - GENERAL IMPORTANCE OF GLIADIN DEAMIDATION FOR INTESTINAL T-CELL RECOGNITION

Coeliac disease probably results from a T-cell response to wheat gliad in and is associated to HLA-DQ2. No gliadin epitopes recognized by int estinal T cells have yet been identified, limiting our understanding o f the pathogenesis. Gut-lesion-derived DQ2-restricted T cells from coe liac disease patients were used to identify an epitope within a purifi ed gamma-type gliadin. The structure of the epitope was characterized by mass spectrometry and verified by synthesis. The epitope (QPQQSFPEQ Q) results from deamidation of a distinct glutamine in the native stru cture. This deamidation is important for binding to DQ2 and T-cell rec ognition. Other gut-derived T cells fail to recognize the epitope, alt hough deamidation of unfractionated gliadin enhances the response of a ll gut-derived DQ2-restricted T cells isolated from several patients. Several DQ2-restricted T cell epitopes exist, but for all of them deam idation of glutamine residues appears to be critical for creation of a ctive epitopes. Native gliadin has few negatively charged residues but is very rich in glutamine. After deamidation gliadin becomes a rich s ource of DQ2 epitopes thus providing a link between DQ2, gliadin and c oeliac disease. The necessity for modification may have general immuno logical relevance.