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Celiacdisease isan intestinalmalabsorptioncharacterizedby an intolerance to cereal proteins accompanied by immuno-logical responses to dietary gliadins and an autoantigen located in the endomysium. The latter has been identified as the enzyme tissue transglutaminase which belongs to a family of enzymes that catalyze protein cross-linking reac-tions and is constitutivelyexpressed inmany tissues aswell as being activated during apoptosis. | Eur. J. Biochem. 269 5175-5181 2002 FEBS 2002 doi 10.1046 j.1432-1033.2002.03215.x The analysis of the fine specificity of celiac disease antibodies using tissue transglutaminase fragments Daniele Sblattero1 Fiorella Florian1 Elisabetta Azzoni1. Trevin Zvla3. Min Park3 Valentina Baldas2 Tarcisio Not2 Alessandro Ventura2 Andrew Bradbury3 4 and Roberto Marzari1 1 Dipartimento di Biologia University of Trieste Trieste Italy 2IRCSS Burlo Garofolo Trieste Italy 3Biosciences Division Los Alamos National Laboratory Los Alamos New Mexico USA 4SISSA Trieste Italy Celiac disease is an intestinal malabsorption characterized by an intolerance to cereal proteins accompanied by immunological responses to dietary gliadins and an autoantigen located in the endomysium. The latter has been identified as the enzyme tissue transglutaminase which belongs to a family of enzymes that catalyze protein cross-linking reactions and is constitutively expressed in many tissues as well as being activated during apoptosis. In a recent paper we described the selection and characterization of anti-transglutaminase Igs from phage antibody libraries created from intestinal lymphocytes from celiac disease patients. In this work using transglutaminase gene fragments we identify a region of tissue transglutaminase recognized by these antibodies as being conformational and located in the core domain of the enzyme. This is identical to the region recognized by anti-transglutaminase Igs found in the serum of celiac disease patients. Keywords autoimmunity celiac disease transglutaminase epitope mapping phage display. Celiac disease CD is a genetic disease strongly linked to HLA DQ2 with other genetic factors also thought to be important. It is characterized by flattening of the intestinal mucosa and malabsorption. The pathogenesis involves dietary exposure to wheat gluten and similar proteins in rye barley and possibly oats 1 with gliadins specific antigenic determinants found in glutens 2 playing a .