title: Heat shock protein 90 (HSP90) contributes to cytosolic translocation of extracellular antigen for cross-presentation by dendritic cells.
abstract: In antigen (Ag) cross-presentation, dendritic cells (DCs) take up extracellular Ag and translocate them from the endosome to the cytosol for proteasomal degradation. The processed peptides can enter the conventional MHC I pathway. The molecules responsible for the translocation of Ag across the endosomal membrane into the cytosol are unknown. Here we demonstrate that heat shock protein 90 (HSP90) is critical for this step. Cross-presentation and -priming were decreased in both HSP90α-null DCs and mice. CD8α(+) DC apoptosis mediated by translocation of exogenous cytochrome c to the cytosol was also eliminated in HSP90α-null mice. Ag translocation into the cytosol was diminished in HSP90α-null DCs and in DCs treated with an HSP90 inhibitor. Internalized Ag was associated with HSP90 and translocated to the cytosol, a process abrogated by the HSP90 inhibitor. Ag within purified phagosomes was released in an HSP90-dependent manner. These results demonstrate the important role of HSP90 in cross-presentation by pulling endosomal Ag out into the cytosol.
authors.affiliation: Laboratories for Immunochaperones, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama 230-0045, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Imai
authors.forename: Yu
authors.initials: Y
authors.lastname: Kato
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kajiwara
authors.forename: Shusaku
authors.initials: S
authors.lastname: Mizukami
authors.forename: Ikuo
authors.initials: I
authors.lastname: Ishige
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ichiyanagi
authors.forename: Masaki
authors.initials: M
authors.lastname: Hikida
authors.forename: Ji-Yang
authors.initials: JY
authors.lastname: Wang
authors.forename: Heiichiro
authors.initials: H
authors.lastname: Udono
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism*; D001692:Biological Transport; D003600:Cytosol / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D000941:Antigens; D018841:HSP90 Heat-Shock Proteins