T cell populations require mechanisms to create a dynamic antigen-response range independently of the initial population size. In eLife, Tkach et al. show that crosstalk between signaling via the TCR and the receptor for IL-2 (IL-2R) and feedback over the time of antigen exposure enable T cell populations of various sizes to respond to a large range of stimuli. TCR signaling inhibits phosphorylation of the transcription factor STAT5 in a manner dependent on the antigen dose (but independent of IL-2R), while phosphorylated STAT5 inhibits IL-2 production but upregulates IL-2Rα expression. In this regulatory-loop setting, inhibition of IL-2 signaling by the TCR is critical for 'scaling' of IL-2 production dependent on the antigen dose but independent of population size. This study suggests that the accumulation of IL-2 is 'scaled' as a function of antigen load and represents a means of reporting that load independently of the number of T cells in the starting monoclonal or polyclonal population.

eLife (9 April 2014) doi:10.7554/eLife.01944