The role of endocytic trafficking in antigen T cell receptor activation

Antigen T cell receptors (TCR) recognize antigenic peptides displayed by the major histocompatibility complex (pMHC) and play a critical role in T cell activation. The levels of TCR complexes at the cell surface, where signaling is initiated, depend on the balance between TCR synthesis, recycling and degradation. Cell surface TCR interaction with pMHC leads to receptor clustering and formation of a tight T cell-APC contact, the immune synapse, from which the activated TCR is internalized. While TCR internalization from the immune synapse has been initially considered to arrest TCR signaling, recent evidence support the hypothesis that the internalized receptor continues to signal from specialized endosomes. Here, we review the molecular mechanisms of TCR endocytosis and recycling, both in steady state and after T cell activation. We then discuss the experimental evidence in favor of endosomal TCR signaling and its possible consequences on T cell activation.