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  CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes

Becker, T., Hartl, F. U., & Wieland, F. (2002). CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes. Journal of Cell Biology, 158(7), 1277-1285.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-6E46-1 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-6E47-0
Genre: Journal Article
Alternative Title : J. Cell Biol.

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 Creators:
Becker, T., Author
Hartl, F. U.1, Author              
Wieland, F., Author
Affiliations:
1Hartl, Franz-Ulrich / Cellular Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565152              

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Free keywords: heat shock protein receptor; immune response; cross priming; co-chaperone; CD40; antigen-presenting cell
 Abstract: Tumor and viral antigens elicit a potent immune response by heat shock protein-dependent uptake of antigenic peptide with subsequent presentation by MHC I. Receptors on antigen- presenting cells that specifically bind and internalize a heat shock protein-peptide complex have not yet been identified. Here, we show that cells expressing CD40, a cell surface protein crucial for B cell function and autoimmunity, specifically bind and internalize human Hsp70 with bound peptide. Binding of Hsp70-peptide complex to the exoplasmic domain of CD40 is mediated by the NH2-terminal nucleotide- binding domain of Hsp70 in its ADP state. The Hsp70 cochaperone Hip, but not the bacterial Hsp70 homologue DnaK, competes formation of the Hsp70-CD40 complex. Binding of Hsp70-ADP to CD40 is strongly increased in the presence of Hsp70 peptide substrate, and induces signaling via p38. We suggest that CD40 is a cochaperone-like receptor mediating the uptake of exogenous Hsp70-peptide complexes by macrophages and dendritic cells.

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Language(s): eng - English
 Dates: 2002-09-30
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 35307
ISI: 000178407500013
 Degree: -

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Title: Journal of Cell Biology
  Alternative Title : J. Cell Biol.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 158 (7) Sequence Number: - Start / End Page: 1277 - 1285 Identifier: ISSN: 0021-9525