Gliadin specific, HLA DQ2-restricted T cells are commonly found in small intestinal biopsies from coeliac disease patients, but not from controls.
The authors have analysed gliadin specific, CD4+ T cells isolated from small intestinal biopsies of 23 adult coeliac disease patients (20 on a gluten-free diet and three untreated) and nine control patients. The biopsies were stimulated ex vivo with a peptic/tryptic digest of gliadin for 24 h, and activated T cells were positively selected with paramagnetic beads coated with an antibody against the interleukin-2 receptor. The T cells were expanded and tested for gliadin reactivity and HLA restriction. Gliadin specific, polyclonal T cell lines were recovered from biopsies of all 23 patients. Inhibition studies of T cell lines from 21 patients with anti-HLA monoclonal antibodies indicated predominant presentation of the gliadin antigen by HLA-DQ2 in T cell lines from 11 patients (lines from seven patients with complete MoAb inhibition, the remaining with incomplete inhibition) and incomplete inhibition by HLA-DR3 in lines from three patients. Nine gliadin specific T cell clones from six patients were established; all of these were HLA-DQ2 restricted. Gliadin specific T cells were not found in biopsies from the non-coeliac controls. Our findings demonstrate that gliadin reactive T cells are commonly found in the intestinal mucosa of CD patients and they support the notion that the majority of T cell recognize gliadin peptide(s) when presented by the disease associated DQ2 molecules.
Molberg
O
O
Institute of Transplantation Immunology, National Hospital, Oslo, Norway.
Kett
K
K
Scott
H
H
Thorsby
E
E
Sollid
L M
LM
Lundin
K E
KE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000938:Antigen-Presenting Cells / Q000276:immunology; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002446:Celiac Disease / Q000276:immunology* / Q000473:pathology; D005260:Female; D005903:Gliadin / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged
D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D005903:Gliadin