title: HLA restriction patterns of gliadin- and astrovirus-specific CD4+ T cells isolated in parallel from the small intestine of celiac disease patients.
abstract: Celiac disease is a common HLA-DQ2-associated enteropathy caused by an abnormal T-cell-mediated immune response to ingested wheat gliadin proteins. We have previously isolated in situ activated mucosal T cells from celiac disease patients and demonstrated that these T cells were gliadin specific and predominantly DQ2 restricted. In contrast to this, gliadin-specific T cells isolated from peripheral blood display a variable HLA restriction pattern, thereby indicating that the skewed DQ restriction of T cells resident in the celiac lesions could be dictated by a preference for DQ-mediated antigen presentation in the mucosa of CD patients. To address this, we analyzed the HLA restriction of T cells recognizing astrovirus, a common gastroentetitis virus, isolated from intestinal mucosa of six celiac disease patients. As an internal control, gliadin-specific T cells were isolated and analyzed in parallel. The gliadin-specific mucosal T cells were marked in their DQ2 restriction, whereas the parallel astrovirus-specific T cells were predominantly restricted by DR molecules. Our data indicate that the repertoire of T cells present in celiac lesions is determined by the priming antigen(s) and not by a skewing in the expression of functional HLA class II isotypes in the disease affected small intestinal mucosa.
authors.affiliation: Institute of Transplantation Immunology, The National Hospital, University of Oslo, Norway.
authors.forename: O
authors.initials: O
authors.lastname: Molberg
authors.forename: K E
authors.initials: KE
authors.lastname: Lundin
authors.forename: E M
authors.initials: EM
authors.lastname: Nilsen
authors.forename: H
authors.initials: H
authors.lastname: Scott
authors.forename: K
authors.initials: K
authors.lastname: Kett
authors.forename: P
authors.initials: P
authors.lastname: Brandtzaeg
authors.forename: E
authors.initials: E
authors.lastname: Thorsby
authors.forename: L M
authors.initials: LM
authors.lastname: Sollid
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002446:Celiac Disease / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002455:Cell Division; D016207:Cytokines / Q000276:immunology; D005260:Female; D005903:Gliadin / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007421:Intestine, Small / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male; D001257:Mamastrovirus / Q000276:immunology*; D010641:Phenotype
chemical_list: D016207:Cytokines; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D006684:HLA-DR Antigens; D005903:Gliadin