Recent insight in the pathophysiology of coeliac disease: relevance to rheumatoid arthritis

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CER8907
2015 Vol.33, N°4 ,Suppl.92
PI 0008, PF 0010
Special Lecture

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PMID: 26457726 [PubMed]

Received: 28/08/2015
Accepted : 01/09/2015
In Press: 12/10/2015
Published: 14/10/2015

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).