Stimulation strength controls the rate of initiation but not the molecular organisation of TCR-induced signalling.

Amongst the different types of cells the body uses to protect itself, killer T cells have an unique role: they can detect and neutralize cells that have been become dangerous for the organism ­ for example, cells which are cancerous or hijacked by viruses. In a healthy organism, T cells circulate through the body in an inactivated state. When a disease emerges, receptors at the surface of the cells can detect elements coming from harmful agents; this stimulation then triggers a molecular cascade inside the T cell that leads to activation. This system is relatively simple, pairing a finite number of receptors with a limited set of internal components. At the same time, the activity of T cells is finely regulated, and their activation tightly controlled: they must kill enough cells to stop the illness without causing excess damage. How this is accomplished is still unclear. A T cell can recognize harmful agents that bind its receptors with differing strengths, but how this variability in stimulation strength affects the signaling processes within the cell is still poorly understood. To investigate this question, Ma et al. used an approach called mass cytometry and analyzed the internal processes of mouse killer T cells receiving different strengths of stimulation. This investigation revealed little change in the patterns of signaling in response to signals of different strength. Instead, what differed was the proportion of T cells that became activated, and how fast this process took place: stronger stimulations led to a larger population of killer T cells being activated more rapidly. Overall, this work sheds light on how killer T cells fine-tune their response to illness using only a simple system to control their activation.