Role of SNX17 in receptor recycling and antigen recognition by T cells. (IRC2P.445)

Abstract A key component in T cell activation is the endosomal recycling of receptors to the cell surface allowing for continual integration of signaling and antigen recognition. Multiple early endosomal associated proteins have been found to interact with T cell surface receptors and play a role in the recycling and transport of these receptors to the cell surface. One endosomal protein possibly involved in T cell receptor transport is sorting nexin 17 (SNX17). SNX17 has been found to bind with receptors involved in T cell activation, but its role in receptor recycling and T cell activation is unknown. Using lentivirus shRNA against SNX17, we have found that the knockdown of the SNX17 protein resulted in fewer T-APC conjugates, lower CD69, TCR, and LFA-1 surface expression, as well as lower overall TCR recycling compared to control T cells. Using immunofluorescence, we have found that SNX17 colocalizes with TCR and localizes to the peripheral-SMAC at the immune synapse in T-APC conjugates. This data suggest that SNX17 plays a synergistic role in the maintenance of normal surface levels of activating receptors and integrins to permit optimum T cell activation at the immune synapse.