Hsp110 and Grp170, members of the Hsp70 superfamily, bind to scavenger receptor-A and scavenger receptor expressed by endothelial cells-I

Eur J Immunol. 2007 Aug;37(8):2268-79. doi: 10.1002/eji.200737127.


Heat shock protein 110 (hsp110) and glucose-regulated protein (grp170) act as anti-cancer vaccines when complexed to tumor antigens by heat shock. It has been proposed that receptors on antigen-presenting cells contribute to HSP-mediated immune responses. Here, we show that hsp110 binds in a receptor-mediated manner to RAW264.7 macrophages, as does grp170. This hsp110/grp170 binding is inhibited by scavenger receptor ligands, suggesting a role for scavenger receptors as binding structures. We examined scavenger receptor class A (SR-A) and scavenger receptor expressed by endothelial cells-I (SREC-I). We show that hsp110/grp170 binds to both SR-A- and SREC-I-expressing CHO cells in a saturable manner and scavenger receptor ligands inhibit binding. Hsp110 also saturably binds mouse bone marrow-derived dendritic cells (bmDC) and is inhibited by scavenger receptor ligands. When an hsp110-rat neu (intracellular domain) heat shock complex vaccine is used to pulse mouse bmDC in vitro, an induction of IFN-gamma secretion is observed by CD8+ T lymphocytes isolated from vaccine-immunized mice. This immune response is inhibited by the application of scavenger receptor ligands to bmDC. Thus, SR-A and SREC-I appear to contribute to the binding of hsp110 and grp170 on APC. Scavenger receptors, in general, contribute to the cross-presentation of hsp110-chaperoned protein antigen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • CHO Cells
  • Cancer Vaccines / immunology*
  • Cricetinae
  • Cricetulus
  • Cross-Priming / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Glycoproteins / immunology*
  • Glycoproteins / metabolism
  • HSP110 Heat-Shock Proteins / immunology*
  • HSP110 Heat-Shock Proteins / metabolism
  • HSP70 Heat-Shock Proteins / immunology*
  • HSP70 Heat-Shock Proteins / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Rats
  • Receptors, Scavenger / immunology*
  • Receptors, Scavenger / metabolism
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Scavenger Receptors, Class F / immunology*
  • Scavenger Receptors, Class F / metabolism


  • Cancer Vaccines
  • Glycoproteins
  • HSP110 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • Receptors, Scavenger
  • Recombinant Proteins
  • Scavenger Receptors, Class F
  • glucose-regulated protein 170