Essential Role of Endogenous Heat Shock Protein 90 of Dendritic Cells in Antigen Cross-Presentation
In: The Journal of Immunology, Jg. 185 (2010-09-01), S. 2693-2700
Online
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Zugriff:
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 HSP90α) revealed the pivotal role of HSP90α 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 HSP90α within DC and cytotoxic T cell immunity.
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Essential Role of Endogenous Heat Shock Protein 90 of Dendritic Cells in Antigen Cross-Presentation
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Autor/in / Beteiligte Person: | Kajiwara, Chiaki ; Imai, Takashi ; Udono, Heiichiro ; Nakai, Akira ; Ichiyanagi, Tomoko ; Nakayama, Toshinori ; Mizukami, Shusaku |
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Zeitschrift: | The Journal of Immunology, Jg. 185 (2010-09-01), S. 2693-2700 |
Veröffentlichung: | The American Association of Immunologists, 2010 |
Medientyp: | unknown |
ISSN: | 1550-6606 (print) ; 0022-1767 (print) |
DOI: | 10.4049/jimmunol.1000821 |
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