title: Hsp110 and Grp170, members of the Hsp70 superfamily, bind to scavenger receptor-A and scavenger receptor expressed by endothelial cells-I.
abstract: 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.
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Facciponte
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Wang
authors.forename: John R
authors.initials: JR
authors.lastname: Subjeck
mesh_terms: D000818:Animals; D016466:CHO Cells; D019496:Cancer Vaccines / Q000276:immunology*; D006224:Cricetinae; D003412:Cricetulus; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006023:Glycoproteins / Q000276:immunology* / Q000378:metabolism; D050957:HSP110 Heat-Shock Proteins / Q000276:immunology* / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D051381:Rats; D051116:Receptors, Scavenger / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D051128:Scavenger Receptors, Class F / Q000276:immunology* / Q000378:metabolism
chemical_list: D019496:Cancer Vaccines; D006023:Glycoproteins; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; D051128:Scavenger Receptors, Class F; C098410:glucose-regulated protein 170