FIGURE 1.

Pathways of TCR endocytosis. Non-engaged and ligand-engaged TCRs are internalized through different types of endocytic routes. The recruitment of different molecular players after TCR engagement induces the activation of distinct endocytic pathways that can be divided in two main groups, clathrin-dependent and clathrin-independent. Endocytic vesicles carrying TCRs internalized at the plasma membrane are incorporated into a network of endosomal compartments defined either by clathrin and the AP2 complex (clathrin-dependent endocytosis) or the membrane-organizing protein flotillins (clathrin-independent endocytosis). Alternatively, engaged TCRs are internalized together with bound pMHC trogocytosed from the APC through a clathrin-independent process. Internalized TCRs can be sorted to early endosomes (EE) and recycled to the plasma membrane through the recycling endosomes, remain associated to signaling endosomes, or traffic through late endosomes/multivesicular bodies (MVB) to the lysosomes for degradation.