Distinct Pathways of Antigen Uptake and Intracellular Routing in CD4 and CD8 T Cell Activation

The mechanisms that allow antigen-presenting cells (APCs) to selectively present extracellular antigen to CD8⁺ effector T cells (cross-presentation) or to CD4⁺ T helper cells are not fully resolved. We demonstrated that APCs use distinct endocytosis mechanisms to simultaneously introduce soluble antigen into separate intracellular compartments, which were dedicated to presentation to CD8⁺ or CD4⁺ T cells. Specifically, the mannose receptor supplied an early endosomal compartment distinct from lysosomes, which was committed to cross-presentation. These findings imply that antigen does not require intracellular diversion to access the cross-presentation pathway, because it can enter the pathway already during endocytosis.