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GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL
Celiac Sprue Research Foundation, Palo Alto, California (T.M., Q.L., G.M.G., C.K.); and Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway (Ø.M., L.M.S.)
Celiac Sprue is a widely prevalent immune disease of the small intestine induced by dietary gluten intake in genetically susceptible individuals. It has been suggested that prolyl endopeptidases (PEPs) may be useful catalysts for gluten detoxification. We have investigated this hypothesis using food-grade gluten as the target antigen, and a combination of mass spectrometry and patient-derived T cells as quantitative assay systems. Spectrometric characterization of physiologically proteolyzed gluten revealed a number of 10 to 50 residue peptides containing known T cell epitopes involved in Celiac Sprue pathogenesis. Several of these peptides were multivalent, suggesting they may be potent triggers of the inflammatory response to gluten in celiac patients. Treatment of proteolyzed gluten with recombinant bacterial PEP decreased the number of potentially immunostimulatory peptides. Substantially reduced immunogenicity was also quantified in 12 of 14 intestinal polyclonal T cell lines from celiac patients. Kinetic investigations using eight T cell clones showed rapid destruction of 
-gliadin epitopes, but less complete processing of 
-gliadin epitopes. Given the difficulty associated with a strict lifelong gluten-exclusion diet, the ability of a single enzyme to greatly reduce the antigenic burden of grocery store gluten reinforces the case for developing oral peptidase therapy against Celiac Sprue.
Address correspondence to: Dr. Chaitan Khosla, Celiac Sprue Research Foundation, 3181 Porter Dr., Palo Alto, CA 94304. E-mail: csrf{at}celiacsprue.org
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