title: Recent insight in the pathophysiology of coeliac disease: relevance to rheumatoid arthritis.
abstract: Coeliac disease (CD) is a T cell mediated inflammatory disorder of the small intestine that affects approximately 1% of the population (1, 2). CD is triggered by gluten ingestion, proteins found in wheat, barley and rye. CD4(+) T cells specific for post-translationally modified gluten peptides bound to the disease-predisposing HLA-DQ2 or HLADQ8 molecules are typically found in patients with CD, explaining the strong association between these HLA-alleles and the occurrence of CD (1, 2). In addition, antibodies specific for modified gluten are also present in patients with CD, implying a role for B to T cell presentation (1). Recent studies have determined the T cell repertoire (TCR) that is utilised by gluten-specific T cells in HLA-DQ2(+) and HLA-DQ8(+) patients and structures between such TCR and HLA-DQ-gluten peptide complexes have been solved (3-7). In HLA-DQ2 patients the TCR repertoire specific for an immunodominant gluten peptide is dominated by the expression of TRAV26 and TRBV7-2 (3-5) while in HLA-DQ8(+) patients such T cells frequently express TRAV26 and TRBV9 (6, 7). Moreover, in the TCR-HLADQ-gluten complexes a non-germline encoded arginine is positioned in the interface between the TCR and HLADQ-gluten which makes critical interactions with both HLA-DQ and the bound peptide (5-7). Collectively, these observations point to stringent selection of a high affinity TCR repertoire in patients with CD. Similar mechanisms are likely to play a role in rheumatoid arthritis (RA).
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. f.koning@lumc.nl.
authors.forename: Frits
authors.initials: F
authors.lastname: Koning
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002446:Celiac Disease / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D005983:Glutens / Q000276:immunology* / Q000378:metabolism; D006683:HLA-DQ Antigens / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D006683:HLA-DQ Antigens; D011948:Receptors, Antigen, T-Cell; D005983:Glutens