Editors' ChoiceImmunology

Flagging the TCR

Sci. Signal.  10 Nov 2009:
Vol. 2, Issue 96, pp. ec360
DOI: 10.1126/scisignal.296ec360

The activation of T cells by antigen-presenting cells (APCs) induces the formation of an interface called the immunological synapse (IS), and polarized recycling of T cell receptor (TCR)-CD3 complexes leads to their enrichment at the IS. During IS formation, the microtubule organizing center (MTOC) of the T cell is repositioned to face the APC so that molecules can be delivered efficiently to the IS. The MTOC also organizes intraflagellar transport (IFT) within the primary cilium, a sensory organ possessed by many cells. Given that hematopoietic cells lack primary cilia, Finetti et al. were surprised to detect IFT20, a component of the IFT system, in T cells in humans and mice. IFT20 associated with the MTOC and Golgi compartments in primary human T cells and in the Jurkat T cell line. When Jurkat cells were incubated with antigen-loaded Raji cells (which acted as APCs), TCR-CD3 complexes clustered at the IS and IFT20 translocated to the IS with the MTOC and Golgi. Whereas knockdown of IFT20 in Jurkat cells did not block translocation of the MTOC or Golgi to the IS, clustering of the TCR-CD3 complex was impaired. Assessment of tyrosine kinase activity showed that TCR signaling was less efficient in IFT20-knockdown cells than in control cells, and IFT20-knockdown cells also exhibited poor recycling of internalized TCR-CD3 complexes compared with that in control cells. In addition, IFT20 was required for the recruitment of other IFT components to the TCR-CD3 complex. Together, these data suggest that components of the IFT system play a role in TCR-CD3 clustering that is independent of their roles in primary cilia.

F. Finetti, S. R. Paccani, M. G. Riparbelli, E. Giacomello, G. Perinetti, G. J. Pazour, J. L. Rosenbaum, C. T. Baldari, Intraflagellar transport is required for polarized recycling of the TCR/CD3 complex to the immune synapse. Nat. Cell Biol. 11, 1332–1339 (2009). [PubMed]