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Contributo in rivista
Tipo: Articolo in rivista
Titolo: Identification of immunodominant epitopes of alpha-gliadin in HLA-DQ8 transgenic mice following oral immunization.
Anno di pubblicazione: 2005
Autori: Senger S.; Maurano F.; Mazzeo M.F.; Gaita M.; Fierro O.; David C.S.; Troncone R.; Auricchio S.; Siciliano R.A.; Rossi M.
Affiliazioni autori: Istituto di Scienze dell’Alimentazione, Consiglio Nazionale delle Ricerche, Avellino, Italy; Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN USA ‡European Laboratory for Food Induced Diseases and Departmentof Pediatrics, University “Federico II” of Naples, Naples, Italy
Abstract: Celiac disease, triggered by wheat gliadin and related prolamins from barley and rye, is characterized by a strong association with HLA-DQ2 and HLA-DQ8 genes. Gliadin is a mixture of many proteins that makes difficult the identification of major immunodominant epitopes. To address this issue, we expressed in Escherichia coli a recombinant alpha-gliadin (r-alpha-gliadin) showing the most conserved sequence among the fraction of alpha-gliadins. HLA-DQ8 mice, on a gluten-free diet, were intragastrically immunized with a chymotryptic digest of r-alpha-gliadin along with cholera toxin as adjuvant. Spleen and mesenteric lymph node T cell responses were analyzed for in vitro proliferative assay using a panel of synthetic peptides encompassing the entire sequence of r-alpha-gliadin. Two immunodominant epitopes corresponding to peptide p13 (aa 120-139) and p23 (aa 220-239) were identified. The response was restricted to DQ and mediated by CD4+ T cells. In vitro tissue transglutaminase deamidation of both peptides did not increase the response; furthermore, tissue transglutaminase catalyzed extensive deamidation in vitro along the entire r-alpha-gliadin molecule, but failed to elicit new immunogenic determinants. Surprisingly, the analysis of the cytokine profile showed that both deamidated and native peptides induced preferentially IFN-gamma secretion, despite the use of cholera toxin, a mucosal adjuvant that normally induces a Th2 response to bystander Ags. Taken together, these data suggest that, in this model of gluten hypersensitivity, deamidation is not a prerequisite for the initiation of gluten responses.
Pagine da: 8087
Pagine a: 8095
The Journal of immunology
Williams & Wilkins,
Numero volume: 175
Indicizzato da: ISI Web of Science (WOS) 
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