4.8 Article

Adhesion shapes T cells for prompt and sustained T-cell receptor signalling

Journal

EMBO JOURNAL
Volume 29, Issue 23, Pages 4035-4047

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2010.258

Keywords

immunological synapse; LFA-1; mitochondria; T-cell polarity

Funding

  1. EMBO
  2. European Community [201106]
  3. E-Rare 2007

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During T-cell migration, cell polarity is orchestrated by chemokine receptors and adhesion molecules and involves the functional redistribution of molecules and organelles towards specific cell compartments. In contrast, it is generally believed that the cell polarity established when T cells meet antigen-presenting cells (APCs) is controlled by the triggered T-cell receptor (TCR). Here, we show that, during activation of human T lymphocytes by APCs, chemokines and LFA-1 establish cell polarity independently of TCR triggering. Chemokine-induced LFA-1 activation results in fast recruitment of MTOC and mitochondria towards the potential APC, a process required to amplify TCR Ca(2+) signalling at the upcoming immunological synapse, to promote nuclear translocation of transcriptional factor NFATc2 and boost CD25 expression. Our data show that the initial adhesive signals delivered by chemokines and LFA-1 shape and prepare T cells for antigen recognition. The EMBO Journal (2010) 29, 4035-4047. doi:10.1038/emboj.2010.258; Published online 15 October 2010

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