Immune synapse targeting of specific recycling receptors by the intraflagellar transport system

Abstract

T cell activation requires sustained signaling at the immune synapse (IS), a specialized interface with the APC that assembles following TCR engagement by MHC-bound peptide. Central to sustained signaling is the continuous IS recruitment of TCRs which are partly mobilized from an endosomal pool by polarized recycling. We have identified IFT20, a component of the intraflagellar transport (IFT) system that controls ciliogenesis, as a central regulator of TCR recycling to the IS. Here we have investigated the interplay of IFT20 with the Rab GTPase network that orchestrates recycling. We found that IFT20 forms a complex with Rab5 and the TCR on early endosomes. IFT20 knockdown resulted in a block of recycling TCRs in Rab5+ endosomes. Recycling of the transferrin receptor, but not of CXCR4, was disrupted by IFT20 deficiency. The IFT components, IFT52 and IFT57, were found to act in concert with IFT20 in regulating TCR and TfR recycling. The results provide novel insights into the mechanisms that control TCR recycling and IS assembly and underscore the trafficking-related function of the IFT system beyond ciliogenesis.