1. Efficient T cell-B cell collaboration guides autoantibody epitope bias and onset of celiac disease.
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Iversen, Rasmus, Roy, Bishnudeo, Stamnaes, Jorunn, Høydahl, Lene S., Hnida, Kathrin, Neumann, Ralf S., Korponay-Szabó, Ilma R., Lundin, Knut E. A., and Sollid, Ludvig M.
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CELIAC disease , *T cells , *RECOMBINANT antibodies , *ANTIGEN presentation , *B cells - Abstract
B cells play important roles in autoimmune diseases through autoantibody production, cytokine secretion, or antigen presentation to T cells. In most cases, the contribution of B cells as antigen-presenting cells is not well understood. We have studied the autoantibody response against the enzyme transglutaminase 2 (TG2) in celiac disease patients by generating recombinant antibodies from single gut plasma cells reactive with discrete antigen domains and by undertaking proteomic analysis of anti-TG2 serum antibodies. The majority of the cells recognized epitopes in the N-terminal domain of TG2. Antibodies recognizing C-terminal epitopes interfered with TG2 cross-linking activity, and B cells specific for C-terminal epitopes were inefficient at taking up TG2-gluten complexes for presentation to gluten-specific T cells. The bias toward N-terminal epitopes hence reflects efficient T-B collaboration. Production of antibodies against N-terminal epitopes coincided with clinical onset of disease, suggesting that TG2-reactive B cells with certain epitope specificities could be the main antigen-presenting cells for pathogenic, gluten-specific T cells. The link between B cell epitopes, antigen presentation, and disease onset provides insight into the pathogenic mechanisms of a T cell-mediated autoimmune condition. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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