title: Gliadin-specific, HLA-DQ(alpha 1*0501,beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients.
abstract: Celiac disease (CD) is most probably an immunological disease, precipitated in susceptible individuals by ingestion of wheat gliadin and related proteins from other cereals. The disease shows a strong human HLA association predominantly to the cis or trans encoded HLA-DQ(alpha 1*0501,beta 1*0201) (DQ2) heterodimer. T cell recognition of gliadin presented by this DQ heterodimer may thus be of immunopathogenic importance in CD. We therefore challenged small intestinal biopsies from adult CD patients on a gluten-free diet in vitro with gluten (containing both gliadin and other wheat proteins), and isolated activated CD25+ T cells. Polyclonal T cell lines and a panel of T cell clones recognizing gluten were established. They recognized the gliadin moiety of gluten, but not proteins from other cereals. Inhibition studies with anti-HLA antibodies demonstrated predominant antigen presentation by HLA-DQ molecules. The main antigen-presenting molecule was established to be the CD-associated DQ(alpha 1*0501, beta 1*0201) heterodimer. The gluten-reactive T cell clones were CD4+, CD8-, and carried diverse combinations of T cell receptor (TCR) V alpha and V beta chains. The findings suggest preferential mucosal presentation of gluten-derived peptides by HLA-DQ(alpha 1*0501, beta 1*0201) in CD, which may explain the HLA association.
authors.affiliation: Institute of Transplantation Immunology, National Hospital, Oslo, Norway.
authors.forename: K E
authors.initials: KE
authors.lastname: Lundin
authors.forename: H
authors.initials: H
authors.lastname: Scott
authors.forename: T
authors.initials: T
authors.lastname: Hansen
authors.forename: G
authors.initials: G
authors.lastname: Paulsen
authors.forename: T S
authors.initials: TS
authors.lastname: Halstensen
authors.forename: O
authors.initials: O
authors.lastname: Fausa
authors.forename: E
authors.initials: E
authors.lastname: Thorsby
authors.forename: L M
authors.initials: LM
authors.lastname: Sollid
mesh_terms: D000595:Amino Acid Sequence; D002446:Celiac Disease / Q000276:immunology*; D005903:Gliadin / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology*; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D005903:Gliadin