Dominance of an alternative CLIP sequence in the celiac disease associated HLA-DQ2 molecule

Design of gliadin peptide analogues with low affinity for the celiac disease associated HLA-DQ2 protein.

The HLA-DQ2.5 receptors bind gluten-derived peptides and present them to the T cells in the intestinal mucosa thus inducing the development of immune responses typical of the celiac disease. On the basis of the X-ray structure of the domain of HLA-DQ2.5 bound to the DQ2.5-glia-α1a epitope, fifteen peptides were designed with the aim of lowering the epitope binding affinity, thus reducing the au...

Peptide Binding to Hla-dq2 and Development of Blocking Agents for the Treatment of Celiac Disease

Structural basis for HLA-DQ2-mediated presentation of gluten epitopes in celiac disease.

Celiac disease, also known as celiac sprue, is a gluten-induced autoimmune-like disorder of the small intestine, which is strongly associated with HLA-DQ2. The structure of DQ2 complexed with an immunogenic epitope from gluten, QLQPFPQPELPY, has been determined to 2.2-A resolution by x-ray crystallography. The glutamate at P6, which is formed by tissue transglutaminase-catalyzed deamidation, is...

HLA-DQ2 and -DQ8 signatures of gluten T cell epitopes in celiac disease.

Celiac disease is associated with HLA-DQ2 and, to a lesser extent, HLA-DQ8. Type 1 diabetes is associated with the same DQ molecules in the opposite order and with possible involvement of trans-encoded DQ heterodimers. T cells that are reactive with gluten peptides deamidated by transglutaminase 2 and invariably restricted by DQ2 or DQ8 can be isolated from celiac lesions. We used intestinal T ...

Function of DQ2 and DQ8 as HLA susceptibility molecules in celiac disease.

Celiac disease (CD) is a malabsorptive disorder of the small intestine. The disease is a unique model for studies of HLA-associated diseases since (a) the disease shows a stringent HLA association; (b) the disease-inducing agent (wheat gluten and related antigens from other cereals) is known; (c) activated, gluten-specific CD4 + T cells in the lamina propria of the small intestine most likely p...