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 of signaling. We show that in the course of the T helper cell-APC interaction, dawn-regulation of triggered TCR leads to extinction of signaling. However, T cells that have been activated by a previous encounter with peptide-pulsed APC and have extinguished signaling can swiftly repolarize towards APC displaying higher antigen concentrations and dedicate their help to these cells. These results demonstrate that TCR down-regulation allows T cells to calibrate their response and dedicate their help to APC Offering the highest stimulus.