Essential role of endogenous heat shock protein 90 of dendritic cells in antigen cross-presentation.
Extracellular HSP90 associated with Ag peptides have been demonstrated to efficiently cross-prime T cells, following internalization by dendritic cells (DCs). In addition, the nature of cell-associated Ags required for cross-priming is implicated as peptides and proteins chaperoned by heat shock protein (HSP). However, the role of endogenous HSP in DCs during cross-presentation remains elusive. In this paper, we show that endogenous HSP90 is essential for cross-presentation of both soluble and cell-associated Ags in DCs. Cross-presentation of soluble OVA and OVA-loaded transporter associated with Ag processing-1-deficient cells by bone marrow-derived DCs and DC-like cell line DC2.4 was profoundly blocked by HSP90 inhibitors, whereas presentation of endogenously expressed OVA was only partially suppressed. Assays using small interfering RNA and heat shock factor-1-deficient DCs (with defective expression of HSP90alpha) revealed the pivotal role of HSP90alpha in cross-presentation. The results suggest that in addition to HSP90 in Ag donor cells, endogenous HSP90 in DCs plays an essential role during Ag cross-presentation and, moreover, points to a link between heat shock factor-1-dependent induction of HSP90alpha within DC and cytotoxic T cell immunity.
Ichiyanagi
Tomoko
T
Laboratory for Immunochaperones, Research Center for Allergy and Immunology, RIKEN, Yokohama Institute, Tsurumi-Ku, Yokohama, Japan.
Imai
Takashi
T
Kajiwara
Chiaki
C
Mizukami
Shusaku
S
Nakai
Akira
A
Nakayama
Toshinori
T
Udono
Heiichiro
H
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D045142:Cross-Priming / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D012995:Solubility
D018841:HSP90 Heat-Shock Proteins; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin