title: Celiac disease association with CD8+ T cell responses: identification of a novel gliadin-derived HLA-A2-restricted epitope.
abstract: One of the diagnostic hallmarks of the histological lesions associated with celiac disease is the extensive infiltration of the small intestinal epithelium by CD8(+) T cells of unknown Ag specificity. In this study, we report recognition of the gliadin-derived peptide (A-gliadin 123-132) by CD8(+) T lymphocytes from celiac patients. A-gliadin 123-132-specific IFN-gamma production and cytotoxic activity were detected in PBMCs derived from patients on gluten-free diet, but not from either celiac patients on gluten-containing diet or healthy controls. In contrast, A-gliadin 123-132-specific cells were isolated from small intestine biopsies of patients on either gluten-free or gluten-containing diets. Short-term T cell lines derived from the small intestinal mucosa and specific for the 123-132 epitope recognized human APC pulsed with either whole recombinant alpha-gliadin or a partial pepsin-trypsin gliadin digest. Finally, we speculate on a possible mechanism leading to processing and presentation of class I-restricted gliadin-derived epitopes in celiac disease patients.
authors.affiliation: Institute of Food Science and Technology, Consiglio Nazionale delle Ricerche, Avellino, Italy. cgianfrani@isa.av.cnr.it
authors.forename: Carmen
authors.initials: C
authors.lastname: Gianfrani
authors.forename: Riccardo
authors.initials: R
authors.lastname: Troncone
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mugione
authors.forename: Elena
authors.initials: E
authors.lastname: Cosentini
authors.forename: Mariateresa
authors.initials: M
authors.lastname: De Pascale
authors.forename: Clementina
authors.initials: C
authors.lastname: Faruolo
authors.forename: Stefania
authors.initials: S
authors.lastname: Senger
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Terrazzano
authors.forename: Scott
authors.initials: S
authors.lastname: Southwood
authors.forename: Salvatore
authors.initials: S
authors.lastname: Auricchio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
mesh_terms: D000293:Adolescent; D000328:Adult; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002446:Celiac Disease / Q000097:blood / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000097:blood / Q000276:immunology*; D005903:Gliadin / Q000097:blood / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000097:blood / Q000276:immunology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
chemical_list: D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D005903:Gliadin