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Molecular and Cellular Biology, November 2007, p. 7718-7726, Vol. 27, No. 21
0270-7306/07/$08.00+0     doi:10.1128/MCB.00180-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

EWI-2/CD316 Is an Inducible Receptor of HSPA8 on Human Dendritic Cells{triangledown}

Sandra Kettner, Frank Kalthoff, Philipp Graf, Elisabeth Priller, Franz Kricek, Ivan Lindley, and Tamás Schweighoffer*

Novartis Institutes for BioMedical Research Vienna, Vienna, Austria

Received 31 January 2007/ Returned for modification 6 July 2007/ Accepted 25 August 2007

The activation of dendritic cells is marked by changes both on their cell surfaces and in their functions. We define EWI-2/CD316 as an early activation marker of dendritic cells upregulated by Toll-like receptor ligands clearly before CD86 and CD83. By expression cloning, human heat shock protein A8 (HSPA8), a member of the hsp70 family, was identified as the ligand for EWI-2. Soluble EWI-2 bound both to cells expressing HSPA8 and also to immobilized HSPA8 protein. Although heat shock proteins are evolutionarily well conserved, other members of this class, including human hsp60 and mycobacterial hsp65, did not bind to EWI-2. The ligation of EWI-2 enhanced the CCL21/SLC-dependent migration of activated mature dendritic cells but attenuated their antigen-specific stimulatory capacities. Important functions of recently activated dendritic cells are thus critically modulated by the newly discovered HSPA8-EWI-2 interaction.

* Corresponding author. Mailing address: Novartis Institutes for Biomedical Research Vienna, Brunnerstraße 59, A-1230 Vienna, Austria. Phone: (43)-1-866-34-462. Fax: (43)-1-866-34-727. E-mail: tamas.schweighoffer{at}novartis.com

{triangledown} Published ahead of print on 4 September 2007.

Molecular and Cellular Biology, November 2007, p. 7718-7726, Vol. 27, No. 21
0270-7306/07/$08.00+0     doi:10.1128/MCB.00180-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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