A finely orchestrated balance between activating and inhibitory signals is fundamental for the ability of the immune system to effectively attack and eliminate pathogenic microbes but to not react against self-antigens. Derangements of this balance underlie the pathogenesis of autoimmune diseases. Conversely, elucidating the mechanisms of this balance may provide rational strategies for manipulating it in order to enhance the efficacy of vaccines and tumor immunotherapy. One of the clearest illustrations of precise regulation is in the generation of effector and regulatory T cells. In order to analyze the mechanisms of this regulation, we have developed a transgenic mouse model in which a single population of T cells reacts against its known cognate antigen in vivo. Here we summarize our studies with this experimental model, illustrating the sequence of T cell responses that develop and attempting to dissect the stimuli that control these responses.