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, down-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.
Valitutti
S
S
Basel Institute for Immunology, Switzerland.
Müller
S
S
Dessing
M
M
Lanzavecchia
A
A
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D016764:Cell Polarity; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
D011948:Receptors, Antigen, T-Cell; D002118:Calcium