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Front Immunol. 2019 Jan 14;9:3115. doi: 10.3389/fimmu.2018.03115. eCollection 2018.

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

Author information

1
Biotechnology Institute Thurgau (BITg) at the University of Konstanz, Kreuzlingen, Switzerland.
2
Konstanz Research School Chemical Biology, Department of Biology, University of Konstanz, Konstanz, Germany.
3
Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
4
Klinikum Konstanz, Konstanz, Germany.

Abstract

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.

KEYWORDS:

CCR7; LFA-1; TCR; ZAP70; chemokine receptor; immunological synapse; integrins

PMID:
30692994
PMCID:
PMC6339918
DOI:
10.3389/fimmu.2018.03115
[Indexed for MEDLINE]
Free PMC Article

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