title: CD40 is a cellular receptor mediating mycobacterial heat shock protein 70 stimulation of CC-chemokines.
abstract: The 70 kDa mycobacterial heat shock protein (Mtb HSP70) stimulates mononuclear cells to release CC-chemokines. We now show that this function of Mtb HSP70, but not human HSP70, is dependent on the cell surface expression of CD40. Deletion of the CD40 cytoplasmic tail abolished, and CD40 antibody inhibited, Mtb HSP70 stimulation of CC-chemokine release. Mtb HSP70 stimulated THP1, KG1 cells, and monocyte-derived dendritic cells to produce RANTES. Specific binding of CD40-transfected HEK 293 cells to Mtb HSP70 was demonstrated by surface plasmon resonance. Coimmunoprecipitation of Mtb HSP70 with CD40 indicates a physical association between these molecules. The results suggest that CD40 is critical in microbial HSP70 binding and stimulation of RANTES production.
authors.affiliation: Peter Gorer Department of Immunobiology, Guy's, King's, and St. Thomas' Medical School, KCL, London, United Kingdom.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: C G
authors.initials: CG
authors.lastname: Kelly
authors.forename: J T
authors.initials: JT
authors.lastname: Karttunen
authors.forename: T
authors.initials: T
authors.lastname: Whittall
authors.forename: P J
authors.initials: PJ
authors.lastname: Lehner
authors.forename: L
authors.initials: L
authors.lastname: Duncan
authors.forename: P
authors.initials: P
authors.lastname: MacAry
authors.forename: J S
authors.initials: JS
authors.lastname: Younson
authors.forename: M
authors.initials: M
authors.lastname: Singh
authors.forename: W
authors.initials: W
authors.lastname: Oehlmann
authors.forename: G
authors.initials: G
authors.lastname: Cheng
authors.forename: L
authors.initials: L
authors.lastname: Bergmeier
authors.forename: T
authors.initials: T
authors.lastname: Lehner
mesh_terms: D001426:Bacterial Proteins; D019013:CD40 Antigens / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis* / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D029968:Escherichia coli Proteins / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007668:Kidney; D008070:Lipopolysaccharides / Q000494:pharmacology; D046911:Macromolecular Substances; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D019013:CD40 Antigens; D002614:Chelating Agents; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; C444642:HSP70 protein, Mycobacterium tuberculosis; D008070:Lipopolysaccharides; D046911:Macromolecular Substances; D019402:Macrophage Inflammatory Proteins; D011993:Recombinant Fusion Proteins; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D002118:Calcium