Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
Milton L Greenberg
Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
Amit Jairaman
Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
Chijioke Akunwafo
Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
Sabrina Leverrier
Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
Ying Yu
Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
Ian Parker
Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States; Department of Neurobiology and Behavior, University of California, Irvine, Irvine, United States
Joseph L Dynes
Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States
Department of Physiology and Biophysics, University of California, Irvine, Irvine, United States; Institute for Immunology, University of California, Irvine, Irvine, United States
Ca2+ influx through Orai1 channels is crucial for several T cell functions, but a role in regulating basal cellular motility has not been described. Here, we show that inhibition of Orai1 channel activity increases average cell velocities by reducing the frequency of pauses in human T cells migrating through confined spaces, even in the absence of extrinsic cell contacts or antigen recognition. Utilizing a novel ratiometric genetically encoded cytosolic Ca2+ indicator, Salsa6f, which permits real-time monitoring of cytosolic Ca2+ along with cell motility, we show that spontaneous pauses during T cell motility in vitro and in vivo coincide with episodes of cytosolic Ca2+ signaling. Furthermore, lymph node T cells exhibited two types of spontaneous Ca2+ transients: short-duration ‘sparkles’ and longer duration global signals. Our results demonstrate that spontaneous and self-peptide MHC-dependent activation of Orai1 ensures random walk behavior in T cells to optimize immune surveillance.
