title: Saturation, competition, and specificity in interaction of heat shock proteins (hsp) gp96, hsp90, and hsp70 with CD11b+ cells.
abstract: Heat shock proteins (hsp(s)) have been postulated to interact with APCs through specific receptors, although the receptors are yet to be identified. Specificity, saturation, and competition are the three defining attributes of a receptor-ligand interaction. We demonstrate here that the interaction of the heat shock proteins gp96 and hsp90 with CD11b+ cells is specific and saturable and that gp96 can compete with itself in gp96-macrophage interaction. Interestingly, the phylogenetically related hsp90 also competes quite effectively with gp96 for binding to macrophages, whereas the unrelated hsp70 does so relatively poorly, although it binds CD11b+ cells just as effectively. These data provide evidence that the heat shock proteins interact with APCs with specificity and for the existence of at least two distinct receptors, one for gp96 and hsp90 and the other for hsp70.
authors.affiliation: Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Binder
authors.forename: M L
authors.initials: ML
authors.lastname: Harris
authors.forename: A
authors.initials: A
authors.lastname: Ménoret
authors.forename: P K
authors.initials: PK
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D001667:Binding, Competitive / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology; D000939:Epitopes / Q000276:immunology / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D016177:Macrophage-1 Antigen / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity / Q000166:cytology; D011485:Protein Binding / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D000939:Epitopes; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D016177:Macrophage-1 Antigen; C052646:sarcoma glycoprotein gp96 rejection antigens; D016650:Fluorescein-5-isothiocyanate