Calcium Signaling Mechanisms in T Lymphocytes

Abstract

Elevation of intracellular free Ca2+ is one of the key triggering signals for T-cell activation by antigen. A remarkable variety of Ca2+ signals in T cells, ranging from infrequent spikes to sustained oscillations and plateaus, derives from the interactions of multiple Ca2+ sources and sinks in the cell. Following engagement of the T cell receptor, intracellular channels (IP3 and ryanodine receptors) release Ca2+ from intracellular stores, and by depleting the stores trigger prolonged Ca2+ influx through store-operated Ca2+ (CRAC) channels in the plasma membrane. The amplitude and dynamics of the Ca2+ signal are shaped by several mechanisms, including K+ channels and membrane potential, slow modulation of the plasma membrane Ca2+-ATPase, and mitochondria that buffer Ca2+ and prevent the inactivation of CRAC channels. Ca2+ signals have a number of downstream targets occurring on multiple time scales. At short times, Ca2+ 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 Ca2+ signals increase the efficiency and specificity of gene activation events. The complexity of Ca2+ signals contains a wealth of information that may help to instruct lymphocytes to choose between alternate fates in response to antigenic stimulation.