title: Immunogenic peptides can be detected in whole gluten by transamidating highly susceptible glutamine residues: implication in the search for gluten-free cereals.
abstract: Tissue transglutaminase (TG2) plays a central role in celiac disease (CD) pathogenesis by strongly enhancing the immunogenicity of gluten, the CD-triggering antigen. By deamidating specific glutamine (Q) residues, TG2 favors the binding of gluten peptides to DQ2/8 molecules and, subsequently, their recognition by cognate T cells. Six peptides were previously identified within wheat gliadin whole extracts by tagging the TG2-susceptible Q residues with monodansylcadaverine (MDC) and nanospray tandem mass spectrometry (nanoESI-MS/MS). The immunogenicity of these peptides was next tested in gliadin-specific T-cell lines established from CD intestinal mucosa. Four peptides, corresponding to known epitopes of α- and γ-gliadins, induced cell proliferation and interferon (IFN)-γ production. Interestingly, one of the two non-T-cell stimulatory peptides corresponded to the 31-49 α-gliadin peptide implicated in the innate immune activation in CD mucosa. This study describes a strategy for identifying immunogenic gluten peptides potentially relevant for CD pathogenesis in protein extracts from wheat and other edible cereals.
authors.affiliation: Institute of Food Sciences-CNR, 83100 Avellino, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Mamone
authors.forename: Alessandra
authors.initials: A
authors.lastname: Camarca
authors.forename: Olga
authors.initials: O
authors.lastname: Fierro
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mazzarella
authors.forename: Francesco
authors.initials: F
authors.lastname: Addeo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Auricchio
authors.forename: Riccardo
authors.initials: R
authors.lastname: Troncone
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: Carmen
authors.initials: C
authors.lastname: Gianfrani
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation / Q000276:immunology*; D002446:Celiac Disease / Q000276:immunology*; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology; D005903:Gliadin / Q000737:chemistry / Q000276:immunology; D005973:Glutamine / Q000737:chemistry; D005983:Glutens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology; D008875:Middle Aged; D010455:Peptides / Q000276:immunology*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D013601:T-Lymphocytes / Q000276:immunology; D053719:Tandem Mass Spectrometry; D011503:Transglutaminases / Q000235:genetics / Q000276:immunology; D014908:Triticum / Q000737:chemistry* / Q000276:immunology; D055815:Young Adult
chemical_list: D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D005973:Glutamine; D005983:Glutens; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins