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▪ Abstract Elevation of intracellular free Ca<sup>2+</sup> is one of the key triggering signals for T-cell activation by antigen. A remarkable variety of Ca<sup>2+</sup> signals in T cells, ranging from infrequent spikes to sustained oscillations and plateaus, derives from the interactions of multiple Ca<sup>2+</sup> sources and sinks in the cell. Following engagement of the T cell receptor, intracellular channels (IP3 and ryanodine receptors) release Ca<sup>2+</sup> from intracellular stores, and by depleting the stores trigger prolonged Ca<sup>2+</sup> influx through store-operated Ca<sup>2+</sup> (CRAC) channels in the plasma membrane. The amplitude and dynamics of the Ca<sup>2+</sup> signal are shaped by several mechanisms, including K<sup>+</sup> channels and membrane potential, slow modulation of the plasma membrane Ca<sup>2+</sup>-ATPase, and mitochondria that buffer Ca<sup>2+</sup> and prevent the inactivation of CRAC channels. Ca<sup>2+</sup> signals have a number of downstream targets occurring on multiple time scales. At short times, Ca<sup>2+</sup> signals help to stabilize contacts between T cells and antigen-presenting cells through changes in motility and cytoskeletal reorganization. Over periods of minutes to hours, the amplitude, duration, and kinetic signature of Ca<sup>2+</sup> signals increase the efficiency and specificity of gene activation events. The complexity of Ca<sup>2+</sup> signals contains a wealth of information that may help to instruct lymphocytes to choose between alternate fates in response to antigenic stimulation. |
