Figure 8. Distinct pathways of intracellular antigen routing in CD4⁺ and CD8⁺ T cell vaccination to Aspergillus fumigatus.

The activation of CD4⁺ and CD8⁺ T cells is contingent upon the nature of the fungal vaccine, the involvement of distinct innate receptor signaling pathways, and the mode of antigen routing and presentation in DCs. Specifically, both soluble fungal antigens and phagocytosed conidia are routed to the endosome/lysosome compartment that is apparently required for adequate processing and presentation of antigens for CD4⁺ T cell activation. At variance with soluble antigens, conidia are diverted from the early endosomes to the Rab14⁺ compartment, required for the alternative MHC class I presentation, through autophagy. MHC class I–restricted CD8⁺, but not MHC class II–restricted CD4⁺, memory T cells failed to be generated in mice with CGD due to defective DC endosomal alkalinization and autophagy, which impeded sorting to the Rab14⁺ compartment. Note that the non-protective fungal antigen Mep1p colocalized rapidly with Rab9 and weakly with Lamp1, a finding suggesting that transporting antigens from late endosome to the TGN prevents adequate processing and presentation of antigens for CD4⁺ T cell activation.