A sharp T-cell antigen receptor signaling threshold for T-cell proliferation

Significance Biochemical signals triggered by the T-cell receptor (TCR) are required for stimulating T cells and can be initiated within seconds. However, a hallmark of T-cell activation, cell division, occurs hours after TCR signaling has begun, implying that T cells require a minimum duration and/or accumulate TCR signaling events to drive proliferation. To visualize the accumulated signaling experienced by T cells, we used a fluorescent reporter gene that is activated by TCR stimulation. This technique showed a threshold between dividing and nondividing T cells for TCR signaling that does not change with stronger or weaker TCR signaling or the presence of growth factor. Together these data may have implications for the development of T-cell–targeted therapies for autoimmunity.