Glutenin is involved in the gluten-driven mucosal T cell response

Gluten ingestion causes coeliac disease in susceptible individuals. Gluten is a heterogeneous mixture of glutenin and gliadin, the latter of which is considered responsible for disease induction. By combining high-performance liquid chromatography purification steps of gluten with a T cell bioassay and mass spectral analyses, we have identified a glutenin peptide (glt04 70 7-742) that activates T cells from the small intestine of a coeliac disease patient and results in the secretion of large amounts of IFN-gamma. The mi nimal T cell stimulatory core of the peptide (residues 724-734) is repetiti vely present in glutenin molecules. Moreover, it was observed that a large number of naturally occurring variants of this peptide are recognized by th e T cells. These data suggest that the large heterogeneity of glutenin prot eins dramatically increases the number of available T cell epitopes. Togeth er, the results provide new insight into the nature of the gluten antigens that lead to coeliac disease and suggest that glutenin, next to gliadin-der ived antigens, may be involved in the disease process.