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CCR7 Is Recruited to the Immunological Synapse, Acts as Co-stimulatory Molecule and Drives LFA-1 Clustering for Efficient T Cell Adhesion Through ZAP70.

  • Laufer JM Biotechnology Institute Thurgau (BITg) at the University of Konstanz, Kreuzlingen, Switzerland.
  • Kindinger I Biotechnology Institute Thurgau (BITg) at the University of Konstanz, Kreuzlingen, Switzerland.
  • Artinger M Biotechnology Institute Thurgau (BITg) at the University of Konstanz, Kreuzlingen, Switzerland.
  • Pauli A Klinikum Konstanz, Konstanz, Germany.
  • Legler DF Biotechnology Institute Thurgau (BITg) at the University of Konstanz, Kreuzlingen, Switzerland.
  • 2019-01-30
Published in:
  • Frontiers in immunology. - 2018
CCR7
LFA-1
TCR
ZAP70
chemokine receptor
immunological synapse
integrins
Animals
CD3 Complex
Cell Adhesion
Cell Communication
Fibroblasts
HEK293 Cells
Healthy Volunteers
Humans
Hybridomas
Immunological Synapses
Jurkat Cells
Lymphocyte Activation
Lymphocyte Function-Associated Antigen-1
Mice
Monocytes
Primary Cell Culture
Receptors, CCR7
T-Lymphocytes
ZAP-70 Protein-Tyrosine Kinase
English The chemokine receptor CCR7 guides T cells and dendritic cells to and within lymph nodes to launch the onset of adaptive immunity. Here, we demonstrate that CCR7 in addition acts as a potent co-stimulatory molecule in T cell activation. We found that antigen recognition and engagement of the TCR results in CCR7 accumulation at the immunological synapse where CCR7 and the TCR co-localize within sub-synaptic vesicles. We demonstrate that CCR7 triggering alone is sufficient to recruit and activate ZAP70, a critical kinase for T cell activation, through Src kinase, whereas TCR CCR7 co-stimulation results in increased and prolonged ZAP70 kinase activity. Finally, we show that ZAP70, acting as adapter molecule, is critical for CCR7-mediated inside-out signaling to integrins, thereby modulating LFA-1 valency regulation to promote cell adhesion, a key step in immunological synapse formation and efficient T cell activation.
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  • English
Open access status
gold
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Persistent URL
https://sonar.ch/global/documents/112614
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