Disruption of positive selection of thymocytes causes autoimmunity

To differentiate into T cells, immature thymocytes must engage, through the ir antigen-specific T-cell receptor, peptides derived from self proteins pr esented by cortical epithelial cells in the thymus, a process called positi ve selection. Despite this requirement for self-recognition during developm ent, mature T cells do not normally show autoreactivity. Mice injected in t he thymus with procainamide-hydroxylamine, a metabolite of procainamide, de velop autoimmune features resembling drug-induced lupus. Here, we show that when thymocytes undergo positive selection in the presence of procainamide -hydroxylamine, they fail to establish unresponsiveness to low affinity sel ecting self antigens, resulting in systemic autoimmunity.