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Istituto di scienza dell'alimentazione

Torna all'elenco Contributi in rivista anno 2009

Contributo in rivista

Tipo: Articolo in rivista

Titolo: Intestinal T cell responses to gluten peptides are largely heterogeneous: implications for a peptide-based therapy in celiac disease.

Anno di pubblicazione: 2009

Formato: Elettronico Cartaceo

Autori: Camarca A, Anderson RP, Mamone G, Fierro O, Facchiano A, Costantini S, Zanzi D, Sidney J, Auricchio S, Sette A, Troncone R, Gianfrani C.

Affiliazioni autori: Camarca A. Istituto di Scienza dell'Alimentazione Anderson RP. Walter & Eliza Hall Inst Med Res, Autoimmun & Transplantat Div, Parkville, Vic, Australia Mamone G. Istituto di Scienza dell'Alimentazione Fierro O. Istituto di Scienza dell'Alimentazione Facchiano A. Istituto di Scienza dell'Alimentazione Costantini S. Istituto di Scienza dell'Alimentazione Zanzi D. Università di Napoli Federico II Sidney J. La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA Auricchio S. Università di Napoli Federico II Sette A. La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA Troncone R. Università di Napoli Federico II Gianfrani C. Istituto di Scienza dell'Alimentazione

Autori CNR:


Lingua: inglese

Abstract: The identification of gluten peptides eliciting intestinal T cell responses is crucial for the design of a peptide-based immunotherapy in celiac disease (CD). To date, several gluten peptides have been identified to be active in CD. In the present study, we investigated the recognition profile of gluten immunogenic peptides in adult HLA-DQ2(+) celiac patients. Polyclonal, gliadin-reactive T cell lines were generated from jejunal mucosa and assayed for both proliferation and IFN-gamma production in response to 21 peptides from wheat glutenins and alpha-, gamma-, and omega-gliadins. A magnitude analysis of the IFN-gamma responses was performed to assess the hierarchy of peptide potency. Remarkably, 12 of the 14 patients recognized a different array of peptides. All a-gliadin stimulatory peptides mapped the 57-89 N-terminal region, thus confirming the relevance of the known polyepitope 33-mer, although it was recognized by only 50% of the patients. By contrast, gamma-gliadin peptides were collectively recognized by the great majority (11 of 14, 78%) of CD volunteers. A 17-mer variant of 33-mer, QLQPFPQPQLPYPQPQP, containing only one copy of DQ2-alpha-I and DQ2-alpha-II epitopes, was as potent as 33-mer in stimulating intestinal T cell responses. A peptide from omega-gliadin, QPQQPFPQPQQPFPWQP, although structurally related to the a-gliadin 17-mer, is a distinct epitope and was active in 5 out of 14 patients. In conclusion, these results showed that there is a substantial heterogeneity in intestinal T cell responses to gluten and highlighted the relevance of gamma- and omega-gliadin peptides for CD pathogenesis. Our findings indicated that alpha-gliadin (57-73), gamma-gliadin (139-153), and omega-gliadin (102-118) are the most active gluten peptides in DQ2(+) celiac patients.

Lingua abstract: inglese

Pagine da: 4158

Pagine a: 4166

Pagine totali: 9


The Journal of immunology Williams & Wilkins,
Paese di pubblicazione: Stati Uniti d'America
Lingua: inglese
ISSN: 0022-1767

Numero volume: 182

DOI: 10.4049/jimmunol.0803181

Referee: Sì: Internazionale

Indicizzato da: ISI Web of Science (WOS) [000264574600028]

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