| First Author | Ichiyanagi T | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 5 | Pages | 2693-700 |
| PubMed ID | 20668218 | Mgi Jnum | J:163264 |
| Mgi Id | MGI:4821512 | Doi | 10.4049/jimmunol.1000821 |
| Citation | Ichiyanagi T, et al. (2010) Essential role of endogenous heat shock protein 90 of dendritic cells in antigen cross-presentation. J Immunol 185(5):2693-700 |
| abstractText | 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. |
