Essential role of endogenous heat shock protein 90 of dendritic cells in antigen cross-presentation

Tomoko Ichiyanagi, Takashi Imai, Chiaki Kajiwara, Shusaku Mizukami, Akira Nakai, Toshinori Nakayama, Heiichiro Udono

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2693-2700
Number of pages8
JournalJournal of Immunology
Volume185
Issue number5
DOIs
Publication statusPublished - Sep 1 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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