Intraflagellar transport is required for polarized recycling of the TCR/CD3 complex to the immune synapse

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Abstract
IFT20, known to control intraflagellar transport during cilia biogenesis, is also expressed in lymphoid and myeloid non-ciliated cells. IFT20 is localized to the secretory pathway in T-lymphocytes and translocates to the immune synapse on antigen engagement to modulate the recycling of T-cell receptors. Most eukaryotic cells have a primary cilium which functions as a sensory organelle1. Cilia are assembled by intraflagellar transport (IFT), a process mediated by multimeric IFT particles and molecular motors2. Here we show that lymphoid and myeloid cells, which lack primary cilia, express IFT proteins. IFT20, an IFT component essential for ciliary assembly3,4, was found to colocalize with both the microtubule organizing centre (MTOC) and Golgi and post-Golgi compartments in T-lymphocytes. In antigen-specific conjugates, IFT20 translocated to the immune synapse. IFT20 knockdown resulted in impaired T-cell receptor/CD3 (TCR/CD3) clustering and signalling at the immune synapse, due to defective polarized recycling. Moreover, IFT20 was required for the inducible assembly of a complex with other IFT components (IFT57 and IFT88) and the TCR. The results identify IFT20 as a new regulator of immune synapse assembly in T cells and provide the first evidence to implicate IFT in membrane trafficking in cells lacking primary cilia, thereby introducing a new perspective on IFT function beyond its role in ciliogenesis.