Heat shock protein 90 targets a chaperoned peptide to the static early endosome for efficient cross‐presentation by human dendritic cells

Cancer Science

Tsutomu Tanaka¹  Koichi Okuya³  Goro Kutomi³  Akari Takaya¹  Toshimitsu Kajiwara¹  Takayuki Kanaseki¹  Tomohide Tsukahara¹  Yoshihiko Hirohashi¹  Toshihiko Torigoe¹  Koichi Hirata³  Yoshiharu Okamoto²  Noriyuki Sato¹ 

[1] Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan;Joint Department of Veterinary Medicine, Tottori University, Tottori, Japan;Department of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan

关键词: Antigen presentation/processing;    dendritic cells;    heat shock protein;    T cells;    tumor immunity;   

DOI  :  10.1111/cas.12570

来源: Wiley

【 摘 要 】

Abstract

The presentation of an exogenous antigen in a major histocompatibility complex class-I- restricted fashion to CD8⁺ T cells is called cross-presentation. Heat shock proteins (HSPs) such as Hsp70, gp96, and Hsp90 have been shown to elicit efficient CTL responses by cross-presentation through an as-yet entirely unknown mechanism. Hsp90 is the most abundant cytosolic HSP and is known to act as a molecular chaperone. We have shown that a tumor antigen peptide complexed with Hsp90 could be cross-presented by dendritic cells (DCs) through an endosomal pathway in a murine system. However, it has not been determined whether human DCs also cross-present an Hsp90–peptide complex and induce peptide-specific CTLs. In this study, we found that an Hsp90–cancer antigen peptide complex was efficiently cross-presented by human monocyte-derived DCs and induced peptide-specific CTLs. Furthermore, we observed that the internalized Hsp90–peptide complex was strictly sorted to the Rab5⁺, EEA1⁺ static early endosome and the Hsp90-chaperoned peptide was processed and bound to MHC class I molecules through an endosome-recycling pathway. Our data indicate that targeting of the antigen to a “static” early endosome by Hsp90 is essential for efficient cross-presentation.

【 授权许可】

CC BY-NC   
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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