SIGNAL EXTINCTION AND T-CELL REPOLARIZATION IN T-HELPER CELL-ANTIGEN-PRESENTING CELL CONJUGATES

We have previously demonstrated that in T cell-antigen-presenting cell (APC) conjugates many T cell receptors (TCR are serially triggered by a few peptide-MHC complexes, resulting in sustained signaling. Here, we investigate the mechanisms that determine the duration and extent o f signaling. We show that in the course of the T helper cell-APC inter action, dawn-regulation of triggered TCR leads to extinction of signal ing. However, T cells that have been activated by a previous encounter with peptide-pulsed APC and have extinguished signaling can swiftly r epolarize towards APC displaying higher antigen concentrations and ded icate their help to these cells. These results demonstrate that TCR do wn-regulation allows T cells to calibrate their response and dedicate their help to APC Offering the highest stimulus.