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CD40-Independent Engagement of Mammalian hsp70 by Antigen-Presenting Cells¹

Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261

CD40 has been suggested previously to be a receptor for mammalian murine hsc73 (hsp70). We have examined, in vitro and in vivo, the role of CD40 in the interaction of murine dendritic cells and macrophages with hsp70, using several independent parameters including cell surface binding, translocation of NF-B, stimulation of release of TNF-, representation of hsp70-chaperoned peptides, and priming of CD8⁺ T cells. The various consequences of hsp70-APC interaction were compared between CD40^+/+ and CD40^–/– mice and were found to be identical in kinetics and magnitude. These data strongly indicate that all known effects of mammalian hsp70 on APCs are mediated in a CD40-independent manner. In light of the earlier demonstration that mycobacterial hsp70 binds murine CD40 and stimulates the APCs through it, our data indicate that CD40 can discriminate between self and mycobacterial hsp70 and is thus a receptor for patterns associated with microbial pathogens.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ The work was supported by start up funds from the Department of Immunology, University of Pittsburgh. Some experiments were performed in the laboratory of Dr. Pramod K. Srivastava.

² Address correspondence and reprint requests to: Robert J. Binder, E1051, BSTWR, 200 Lothrop Street, Pittsburgh, PA 15261. E-mail address: rjb42{at}pitt.edu

³ Abbreviations used in this paper: HSP, heat shock protein; DC, dendritic cell; RAP, receptor associated protein; PEC, peritoneal exudates cell; hsp70, murine hsc73; sCD40, soluble CD40.