Celiac disease is a chronic inflammatory condition of the small intestine with autoimmune features characterized by CD4+ TH cell reactivity against dietary gluten proteins or related proteins from barley and rye. The disease has a strong HLA association where about 90-95% of the patients express HLA-DQ2.5, and clinically manifests by gut epithelial cell destruction and generation of autoantibodies against transglutaminase 2 (TG2). Active intestinal inflammation is associated with alterations in the composition of antigen presenting cell (APC) subsets compared to healthy controls. This suggests that different APC populations might have distinct functions in the pathogenesis of the disease.
We have isolated and characterized antibodies with specificities against two of the immunodominant gluten epitopes, DQ2.5-glia-α1a and DQ2.5-glia-α2, in complex with HLA-DQ2.5. The selected candidates show unique fine-specificity with ability to distinguish between highly similar pMHC complexes. We have further utilized the DQ2.5:DQ2.5-glia-α1a-specific antibody to characterize antigen presentation using intestinal biopsies from patients and healthy controls.
Our findings demonstrate the utility of this reagent in studies of antigen presentation, and open a possibility for improved patient stratification.