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- Targeting the gluten specific T cell response, a novel therapeutic approach in coeliac disease
Targeting the gluten specific T cell response, a novel therapeutic approach in coeliac disease
Professor Frits Koning
Professor Frits Koning has worked at Leiden University Medical Centre (LUMC), since 1993. He is the Chairman of the scientific advisory board of the LUMC and the Chief Executive Officer of the Dutch Celiac Disease Consortium in which immunologists, geneticists, food specialists and medical doctors collaborate with industrial partners to improve the quality of life of patients with coeliac disease. He is well recognised for his contributions to the field of immune mediated disorders, coeliac disease in particular. Through his work it is now well established which gluten fragments cause disease and how they are recognised by disease related T cells, providing a molecular basis for the genetic association between HLA-DQ and coeliac disease. He has investigated the use of enzymes to detoxify gluten. In his most recent work he uses high dimensional flow cytometry to unravel the involvement of the innate and adaptive immune system in inflammatory bowel disease and coeliac disease.
There is overwhelming evidence that T cell responses specific for gluten peptides bound to HLA-DQ2 and/or HLA-DQ8 in the small intestinal lamina propria are disease causative. Various approaches have been proposed to counteract the deleterious effects of gluten, including enzymatic degradation of gluten, blocking of the peptide presenting capacity of HLA-DQ2/8 and peptide vaccination. Ideally, one would like to eliminate the disease causative T cells as this would represent a likely cure for the disease. Recent work has shown that the T cell response to immunodominant gluten peptides is remarkably similar among patients and highly biased as it is dominated by a restricted T cell receptor usage. Moreover, structural studies have revealed the molecular basis for this biased usage. This combined knowledge offers a novel opportunity to interfere in the disease process as it allows the design of compounds that specifically target the disease causative T cell receptors. By coupling such compounds with toxins it may become possible to eradicate the disease causative T cells without interfering with the normal function of the immune system. The rationale and feasibility of this novel approach will be discussed.