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Coeliac disease (CD), the most common food sensitive enteropathy in humans, is caused by permanent intolerance for dietary gluten.1 2 Typical symptoms include chronic diarrhoea, abdominal distension, and failure to thrive. These symptoms are the result of a lesion in the upper small bowel characterised by (sub)total villous atrophy, hypertrophic crypts, an increased number of interepithelial lymphocytes, and a chronic inflammatory response of the lamina propria lymphocytes. IgA antibodies against endomysium are specific indicators of CD.3 4 Yet CD is considered to be primarily a T cell mediated disease because the majority of patients express the HLA-DQ2 [DQ(α1*0501, β1*02)], and/or −DQ8 [DQ(α1*03, β1*0302)] molecules5 6; gluten specific HLA-DQ restricted T cells are present at the site of the lesion in the gut7 and withdrawal of gluten stops the disease process.2 The identity of potentially disease inducing, gluten derived T cell stimulatory peptides, however, was unknown until recently.
Here we briefly discuss recent work which sheds light on the requirements for an optimal interaction between gluten, HLA-DQ, and T cells, requirements which explain the association of CD with HLA-DQ2/8.
Specificity of the humoral immune response
CD patients generally have high serum levels of antigliadin antibodies. A more specific indicator for the disease, however, is the presence of antiendomysium antibodies.3 4 Recently, these antibodies have been found to be specific for the enzyme tissue transglutaminase (tTG).8 tTG is a ubiquitous protein that belongs to a family of structurally and functionally related calcium dependent enzymes. These enzymes cross link proteins by catalysing the formation of isopeptide bonds between γ carboxamide groups of glutamine residues and ε amino groups of lysine residues.9 10 An important function of tTG is thought to be cross linking of extracellular matrix proteins which stabilises damaged tissue10 11 but other activities have also been identified. …
Footnotes
- Abbreviations used in this paper:
- CD
- coeliac disease
- tTG
- tissue transglutaminase
- TGF-β
- transforming growth factor β