title: Characterization of a receptor for heat shock protein 70 on macrophages and monocytes.
abstract: Heat shock proteins (Hsps) and molecular chaperones isolated from tumors or virally infected cells elicit an efficient CD8+ T cell response against bound antigenic peptides. This immune response is mediated by presentation of the peptides on MHC class I complexes of antigen-presenting cells (APCs), but the cellular mechanism of this presentation process is not yet understood. Here we provide evidence for the existence of a proteinaceous receptor on the surface of APCs that is specific for mammalian Hsp70. Using a flow cytometry-based assay, saturable binding of Hsp70 to the cell surface of macrophages and peripheral blood monocytes, but not of lymphocytes, can be demonstrated. The affinity of the receptor is in the sub-micromolar range (Kd < 100 nM). Only mammalian Hsc70/Hsp70, but not bacterial Hsp70, is bound with high affinity. Subsequent to binding, Hsp70 is taken up by endocytosis, resulting in an intracellular localization. Our results suggest that receptor-mediated endocytosis forms the basis for the demonstrated efficacy of Hsp70-peptide complexes as anti-tumor vaccines.
authors.affiliation: Abteilung Zelluläre Biochemie, Max-Planck-Institut für Biochemie, Martinsried, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Sondermann
authors.forename: T
authors.initials: T
authors.lastname: Becker
authors.forename: M
authors.initials: M
authors.lastname: Mayhew
authors.forename: F
authors.initials: F
authors.lastname: Wieland
authors.forename: F U
authors.initials: FU
authors.lastname: Hartl
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D004705:Endocytosis; D010450:Endopeptidases / Q000494:pharmacology; D005434:Flow Cytometry; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D008214:Lymphocytes / Q000737:chemistry; D008264:Macrophages / Q000737:chemistry*; D051379:Mice; D009000:Monocytes / Q000737:chemistry*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
chemical_list: D018840:HSP70 Heat-Shock Proteins; D011956:Receptors, Cell Surface; D010450:Endopeptidases