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Figure 1 .
HLA class II peptide binding and effect of tissue transglutaminase (tTG). (A) HLA class II allele specific peptide binding. The side chains of particular amino acids in the class II bound peptide make contact with pockets in the class II molecule. The size, shape, and position of these pockets differ between class II alleles. As a result different class II alleles bind a different peptide repertoire. (B) Because of the activity of tTG, the glutamine (Q) residues at p1 and p9 in the HLA-DQ8 bound gliadin peptide are converted to glutamic acid (E) residues which fit tightly into the p1 and p9 pockets of the HLA-DQ8 molecule. The resulting higher binding affinity increases T cell reactivity.
Figure 2 .
Transglutaminase (tTG) is involved in the initiation and/or amplification of the gluten specific T cell response. Gluten derived peptides are absorbed from the lumen of the gut and are subsequently presented to mucosal CD4+ T cells in the lamina propria (LPL). Secretion of a diverse set of inflammatory cytokines by these activated T cells could directly be involved in the destruction of the gut mucosa. Alternatively, the release of so-called secondary inflammatory mediators such as nitric oxide and metalloproteinases by macrophages and mesenchymal cells might be responsible for the coeliac lesion. On tissue damage, release of tTG takes place. tTG mediated deamidation of gluten increases T cell reactivity due to creation of ligands with a high binding affinity for DQ2/DQ8 molecules. Alternatively, as small amounts of tTG are present in the extracellular environment, the initial T cell activation might also be caused by the deamidated gluten antigens. APC, antigen presenting cell; IEL, intraepithelial lymphocyte.