Our finding that miR‐21 sets the correct level of PTEN expression in response to CD28 costimulation, permitting T‐cell response to weak TCR signals, fits well with this framework and provides new mechanistic link between CD28 costimulation, the response to low‐affinity self‐antigens and the equilibrium between self‐tolerance and autoimmunity. The gene discussed is CD28; the disease is Autoimmunity.