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Contributo in rivista
Tipo: Articolo in rivista
Titolo: Design of peptide-based immunotherapy and diagnostics for celiac disease based upon comprehensive, quantitative mapping of T-cell epitopes in gluten. Science Translational Medicine. 2010; 2:41.
Anno di pubblicazione: 2010
Autori: Tye-Din J, Stewart J, Dromey J, Beissbarth T, van Heel D, Tatham A, Henderson K, Mannering S, Gianfrani C, Jewell D, Hill A, McCluskey J, Rossjohn J, and Anderson R.
Affiliazioni autori: 1Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia. 2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia. 3Department of Gastroenterology, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050, Australia. 4Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK. 5Cardiff School of Health Sciences, University of Wales Institute, Cardiff CF5 2YB, UK. 6Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia. 7Institute of Food Science, National Research Council, Via Roma 52, 83100 Avellino, Italy. 8Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DU, UK. 9Jenner Institute, University of Oxford, Oxford OX3 9DU, UK. 10Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
Abstract: Celiac disease is a genetic condition that results in a debilitating immune reaction in the gut to antigens in grain. The antigenic peptides recognized by the T cells that cause this disease are incompletely defined. Our understanding of the epitopes of pathogenic CD4+ T cells is based primarily on responses shown by intestinal T cells in vitro to hydrolysates or polypeptides of gluten, the causative antigen. A protease-resistant 33-amino acid peptide from wheat a-gliadin is the immunodominant antigen, but little is known about the spectrum of T cell epitopes in rye and barley or the hierarchy of immunodominance and consistency of recognition of T cell epitopes in vivo. We induced polyclonal gluten-specific T cells in the peripheral blood of celiac patients by feeding them cereal and performed a comprehensive, unbiased analysis of responses to all celiac toxic prolamins, a class of plant storage protein. The peptides that stimulated T cells were the same among patients who ate the same cereal, but were different after wheat, barley, and rye ingestion. Unexpectedly, a sequence from w-gliadin (wheat) and C-hordein (barley) but not a-gliadin was immunodominant regardless of the grain consumed. Furthermore, T cells specific for just three peptides accounted for most gluten-specific T cells, and their recognition of gluten peptides was highly redundant. Our findings show that pathogenic T cells in celiac disease show limited diversity and therefore suggest that peptide-based therapeutics for this disease and potentially other strongly human leukocyte antigen-restricted immune diseases should be possible.
Lingua abstract: inglese medio (1100-1500)
Pagine da: 1
Pagine a: 14
Pagine totali: 14
Journal of translational medicine
Numero volume: 2:41
Numero fascicolo: 41ra51
Referee: Sì: Internazionale
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