YOU ARE NOW CONNECTED TO THE TOXLINE (1981 FORWARD, NON-ROYALTY) FILE. ==PEPTIDES AND GLUTEN/ CELIAC DISEASE== 1 AUTHOR Tighe MR AUTHOR Ciclitira PJ TITLE The gluten-host interaction. SOURCE Baillieres Clin Gastroenterol; VOL 9, ISS 2, 1995, P211-30 (REF: 42) ABSTRACT Work continues to progress in the unravelling of the molecular interactions involved in the pathogenesis of coeliac disease. The immunogenetics of the disease implicate certain HLA DQ alleles as necessary for subsequent disease development. These HLA molecules have been shown to be necessary in the binding and presentation of gliadin peptides to antigen-specific T cells. Current work is examining the precise HLA-antigen interaction that may lead to the development of antigen-blocking agents. The isolation of antigen-specific T cells has led to the confirmation of a toxic T-cell epitope of the gliadin protein (residues 31-49) and it would appear likely that additional toxic epitopes may be similarly characterized in the near future. No common TCR motifs have so far been detected, although these may become apparent as this work progresses. The gliadin peptide sequence, residues 31-49, has now been demonstrated to be toxic in vivo. Additional toxic T-cell epitopes may also be present within gliadins, but this identification of a toxic gliadin sequence for the first time raises the possibility of future manipulation of the wheat genome (and other toxic cereals) that could lead to the development of new graminae cereals with the properties of wheat, but which do not induce toxicity in patients with coeliac disease. 2 AUTHOR Ellis HJ AUTHOR Doyle AP AUTHOR Wieser H AUTHOR Sturgess RP AUTHOR Day P AUTHOR Ciclitira PJ TITLE Measurement of gluten using a monoclonal antibody to a sequenced peptide of alpha-gliadin from the coeliac-activating domain I. SOURCE J Biochem Biophys Methods; VOL 28, ISS 1, 1994, P77-82 ABSTRACT A monoclonal antibody, raised against a sequenced 54 amino-acid peptide from the coeliac-activating N-terminal region of alpha-gliadin, was used in an assay for the measurement of gluten in foods. A double-sandwich ELISA using a polyclonal capture antibody produced standard curves for unfractionated gliadin and its alpha, beta, gamma and omega subfractions, and for rye, barley and oat prolamins. The sensitivity of the assay for unfractionated gliadin and rye prolamins was 15 ng/ml, for barley and oat prolamins 125 and 250 ng/ml, respectively. Prolamins from coeliac non-toxic rice, maize, millet and sorghum did not cross-react in the assay. 3 AUTHOR Auricchio S AUTHOR De Ritis G AUTHOR De Vincenzi M AUTHOR Silano V TITLE Toxicity mechanisms of wheat and other cereals in celiac disease and related enteropathies. SOURCE J Pediatr Gastroenterol Nutr; VOL 4, ISS 6, 1985, P923-30 (REF: 88) ABSTRACT This paper is a critical appraisal of current theories on the mechanisms of toxicity of wheat and other cereals in celiac disease and some related enteropathies. The "peptidase deficiency," "primary immune defect," and "gluten-lectin" theories on celiac disease are examined and critically discussed on the basis of the relevant data available in 88 references. Special attention has been paid in this review to the nature of the cereal components triggering the appearance of toxic symptoms and signs in celiac disease as well as to underlying action mechanisms. The gluten-lectin theory is the one best able to explain, in addition to celiac disease, some secondary intolerances that may occur in temporarily predisposed individuals as a consequence of several causes, including viral hepatitis and intestinal infections, as well as the occurrence of intestinal lesions in healthy subjects administered very high amounts of gluten. 4 AUTHOR Huebner FR AUTHOR Lieberman KW AUTHOR Rubino RP AUTHOR Wall JS TITLE Demonstration of high opioid-like activity in isolated peptides from wheat gluten hydrolysates. SOURCE Peptides; VOL 5, ISS 6, 1984, P1139-47 ABSTRACT Because of a possible relationship between schizophrenia and celiac disease, a condition in some individuals who are sensitive to wheat gluten proteins in the diet, there has been interest in observations that peptides derived from wheat gluten proteins exhibit opioid-like activity in in vitro tests. To determine the origin of the peptides exhibiting opioid activity, wheat proteins were fractionated by size (gel filtration), by charge differences (ion exchange chromatography) and by differences in hydrophobicity (reversed-phase HPLC). These fractions were hydrolyzed by pepsin or pepsin and trypsin and the resulting peptides separated by gel filtration chromatography. The separated peptides were tested for opioid-like activity by competitive binding to opioid receptor sites in rat brain tissue in the presence of tritium-labeled dihydromorphine. The peptides showed considerable differences in activity; while some peptides exhibited no activity, 0.5 mg of the most active peptides were equivalent to 1 nM of morphine in the binding assay. The most active peptides were derived from the gliadin fraction of the gluten complex. 5 AUTHOR Fluge G AUTHOR Aksnes L TITLE Autoradiographic localization of a gluten peptide during organ culture of human duodenal mucosa. SOURCE J Pediatr Gastroenterol Nutr; VOL 2, ISS 3, 1983, P452-8 ABSTRACT An 125I-labeled subfraction of Frazer's fraction III (molecular weight, 8,000) was added to the culture medium during organ culture of duodenal biopsies from two patients with celiac disease in exacerbation. The isotope-labeled gluten peptide was localized by autoradiography after 6, 12, and 24 h of culture. At 6 h, labeling was located mainly in the basal layers of the biopsies. The tissue was well preserved. After 12 h in culture, the labeling had spread to the lamina propria and the crypts. A few grains were located over enterocytes and desquamated cells. Moderate histological signs of toxicity were observed. After 24 h, there was marked toxic deterioration, comparable to that seen after culture with alpha-gliadin. Labeling had spread throughout the entire section. There seemed to be no specificity of the binding, for the entire section was affected. Culture with the identical gluten fraction, in the radionegative state, produced histological deterioration comparable to that seen after exposure to the isotope-labeled peptide. Gluten peptides are presented to the target cells in a unique way during organ culture, different from in vivo conditions. This may influence the results when the organ culture method is used to investigate the pathogenesis of celiac disease. 6 AUTHOR Wieser H AUTHOR Springer G AUTHOR Belitz HD AUTHOR Ashkenazi A AUTHOR Idar D TITLE Toxicity of different wheat gliadins in coeliac disease. SOURCE Z Lebensm Unters Forsch; VOL 175, ISS 5, 1982, P321-6 ABSTRACT To determine the toxic effect of different gliadins on coeliac patients, which has been variably assessed in the literature, wheat prolamines (gliadin) were separated into the main fractions alpha-, beta-, gamma-, and omega-gliadins by chromatography on Sulfopropyl Sephadex C-50. The chemical compositions of the gliands were characterized by polyacrylamide gel electrophoresis, amino-acid analysis, determination of amide nitrogen and peptide maps. The peptide fractions B2 and B3 were isolated from the gliadins by a peptic tryptic digestion, ultrafiltration and gel filtration on Sephadex G-50. The gliadins and the peptide fractions were examined for coeliac activity by immunological tests (LIF tests) and by organ-culture tests. The results show that the peptide fractions are generally more active than their respective gliadins. The peptide fractions of all gliadins have a coeliac-specific toxic effect; their activities correlate with the chemical composition of the gliadins.