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

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Frontiers in Immunology. 2019, 9, 3115. eISSN 1664-3224. Available under: doi: 10.3389/fimmu.2018.03115
Zusammenfassung

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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ISO 690LAUFER, Julia M., Ilona KINDINGER, Marc ARTINGER, Andreas PAULI, Daniel F. LEGLER, 2019. CCR7 Is Recruited to the Immunological Synapse, Acts as Co-stimulatory Molecule and Drives LFA-1 Clustering for Efficient T Cell Adhesion Through ZAP70. In: Frontiers in Immunology. 2019, 9, 3115. eISSN 1664-3224. Available under: doi: 10.3389/fimmu.2018.03115
BibTex
@article{Laufer2019-01-14Recru-44913,
  year={2019},
  doi={10.3389/fimmu.2018.03115},
  title={CCR7 Is Recruited to the Immunological Synapse, Acts as Co-stimulatory Molecule and Drives LFA-1 Clustering for Efficient T Cell Adhesion Through ZAP70},
  volume={9},
  journal={Frontiers in Immunology},
  author={Laufer, Julia M. and Kindinger, Ilona and Artinger, Marc and Pauli, Andreas and Legler, Daniel F.},
  note={Article Number: 3115}
}
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