Heat shock protein 90 (HSP90) contributes to cytosolic translocation of extracellular antigen for cross-presentation by dendritic cells

被引:125
作者
Imai, Takashi [1 ]
Kato, Yu [1 ]
Kajiwara, Chiaki [1 ]
Mizukami, Shusaku [1 ,3 ]
Ishige, Ikuo [4 ]
Ichiyanagi, Tomoko [1 ]
Hikida, Masaki [5 ]
Wang, Ji-Yang [2 ]
Udono, Heiichiro [1 ,3 ]
机构
[1] RIKEN Yokohama Inst, RCAI, Lab Immunochaperones, Yokohama, Kanagawa 2300045, Japan
[2] RIKEN Yokohama Inst, RCAI, Lab Immune Divers, Yokohama, Kanagawa 2300045, Japan
[3] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Immunol, Okayama 7008558, Japan
[4] BM Equipment Co Ltd, Tokyo 1130034, Japan
[5] Kyoto Univ, Grad Sch Med, Ctr Innovat Immunoregulat Technol & Therapeut, Kyoto 6068501, Japan
关键词
chaperone; knock out mouse; cross-priming; Image Stream; antigen processing; ENDOPLASMIC-RETICULUM; RETRO-TRANSLOCATION; CHAPERONE HSP90; T-CELLS; PEPTIDES; IMMUNITY; HEAT-SHOCK-PROTEIN-90; DEGRADATION; RECEPTOR; COMPLEX;
D O I
10.1073/pnas.1108372108
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 HSP90 alpha-null DCs and mice. CD8 alpha(+) DC apoptosis mediated by translocation of exogenous cytochrome c to the cytosol was also eliminated in HSP90 alpha-null mice. Ag translocation into the cytosol was diminished in HSP90 alpha-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.
引用
收藏
页码:16363 / 16368
页数:6
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