Gliadin peptide specific intestinal T cells in coeliac disease.

espite its heterogeneous clinical appearance, coeliac disease has a remarkable uniform human leuco-cyte antigen (HLA) association. The majority of coeliac disease patients carry a certain variant of HLA-DQ2, the rest carry HLA-DQ8. 1 2 As the physiological role of the HLA system is to present pep-tide fragments of antigens to T cells, it would seem logical that the HLA-DQ2 and HLA-DQ8 molecules predispose to coeliac disease by presenting peptides to T cells in the intestinal mucosa. The pep-tides these T cells recognise could derive form gluten peptides as coeliac disease is precipitated by intestinal exposure to wheat gluten and related proteins of other cereals. In fact, this simple concept has gained substantial experimental evidence in recent years. 1 2 A paper in this issue of Gut 3 adds further credence to this model [see page 212]. The small intestinal lesion is charac-terised by inflammation and infiltration of T cells both in the lamina propria and epithelium. Intraepithelial T cells are typical of coeliac disease but their significance is uncertain and they are unlikely to recognise gluten presented by HLA-DQ2. They may represent an innate (" primitive ") immune response to glu-ten. Their lamina propria counterparts however are much more likely to be key players. In the lamina propria, we find CD4 + T cells and dendritic cell type of antigen presenting cells expressing HLA-DQ2. Therefore, when we first isolated gluten reactive T cells some 10 years ago from the small intestinal mucosa of coe-liac disease patients, some of us hoped that an immediate solution to several conceptual problems was at hand. 4 It turned out to be a bit more complex. Following years of work from a small handful of devoted laboratories, we understand several details with respect to these T cells and what they recognise. We know of several of the peptide epitopes involved in the disease. T cell recognition of many, but not all, is dependent on the action of the small intestinal enzyme tissue transglutami-nase which converts glutamine residues in gluten to glutamic acid. It is in this field that the research group of Professor Ciclitira at St Thomas' Hospital has spent some years of work. It is therefore reassuring that they now report results that are in keeping with previous observations. 3 Four adult coe-liac disease patients were examined and small intestinal biopsies were challenged ex vivo with gluten. Thereafter, a cell suspension was made and …