Celiac Sprue is an autoimmune disease of the small intestine induced by exposure to dietary gluten, but the molecular trigger for gluten toxicity remains unclear. In September 27 Science, Lu Shan and colleagues at Stanford University, Stanford, USA, show that a 33-mer peptide has several characteristics suggesting it is the primary initiator of the inflammatory response to gluten in Celiac Sprue patients (Science, 297:2275-2279, September 27, 2002).

Shan et al. used liquid chromatography coupled with mass and ultraviolet spectroscopy and identified a proteolitic fragment of gliadin, which remained intact despite prolonged exposure to gastric, pancreatic and intestinal proteases. The peptide reacted with tissue transglutaminase — the major autoantigen in Celiac Sprue — and was a potent inducer of gut-derived human T cell lines from 14 of 14 Celiac Sprue patients tested. In addition, in vitro and in vivo assays showed that the peptide could be detoxifed...

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