HSP70 and HSP90 Differentially Regulate Translocation of Extracellular Antigen to the Cytosol for Cross-Presentation

Figure 7

Model illustrating how HSP70 and HSP90 regulate cross-presentation and endogenous Ag presentation. In cross-presentation, internalized exogenous Ag is unfolded within the endosome and translocated through a putative translocon Sec61 complex into the cytosol. The translocation is facilitated by HSP90 but limited by HSP70. The translocated proteins are forwarded to the proteasome for degradation in HSP70-dependent manner. Ag-derived peptides generated by the proteasome enter the same endosome from which it dislocates to the cytosol through TAP molecules and associate with MHCI molecules. TAP molecules and MHCI molecules within the endosome are probably recruited from the endoplasmic reticulum (ER) in a Sec22b-dependent manner. In endogenous Ag presentation, a portion of newly synthesized, unfolded proteins are transported to the proteasome for their degradation by HSP70. Generated peptides enter the ER to associate with MHCI molecules.