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

Article Authors:Alessandra Camarca; Robert P Anderson; Gianfranco Mamone; Olga Fierro; Angelo Facchiano; Susan Costantini; Delia Zanzi; John Sidney; Salvatore Auricchio; Alessandro Sette; Riccardo Troncone; Carmen Gianfrani
Article Title:Intestinal T cell responses to gluten peptides are largely heterogeneous: implications for a peptide-based therapy in celiac disease.
Reference Detail
Reference ID:1014859
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 alpha-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 alpha-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.
Affiliations:Institute of Food Sciences-National Research Council, Avellino, Italy.
Reference Type:Literature
PubMed ID:19299713
Journal:J Immunol
Journal Volume:182
Article Pages:4158-66
Journal ISSN:0022-1767
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@33468f9e;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@5d7ee85e;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@36c9a346;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@6ffe64c3;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@268977a6;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@b0e470e
Article MeSH List:Adolescent; Adult; Amino Acid Sequence; Celiac Disease(immunology); Chromatography, High Pressure Liquid; Female; Gliadin(genetics; immunology); Glutens(immunology); HLA-DQ Antigens; Humans; Interferon-gamma(immunology); Intestinal Mucosa(immunology); Male; Middle Aged; Molecular Sequence Data; Peptide Fragments(immunology); T-Lymphocytes(immunology)
Curation Last Updated:2015-01-17 22:26:37