title: Heat shock proteins 70 and 60 share common receptors which are expressed on human monocyte-derived but not epidermal dendritic cells.
abstract: Priming of CTL by means of heat shock proteins (hsp) is dependent on antigen-presenting cells (APC), which present the hsp-associated peptides, via their cell surface MHC class I molecules, toCD8(+) T cells. It has not yet been established how human (hu) hsp70 interacts with the major (hu)APC, the dendritic cells (DC). Here we show that (hu)hsp70 is specifically internalized intoCD14(-), Toll-like receptor 4(-) monocyte-derived (hu)DC by receptor-mediated endocytosis. We further demonstrate that (hu)hsp70 and (hu)hsp60 share the same receptors on (hu)monocyte-derived DC. Both molecules as well as MHC class I molecules are spontaneously internalized and reach the MHC class II-enriched compartments. Finally, freshly isolated (hu) epidermal Langerhans cells (LC), the DC of the skin, as well as CD34(+)-derived LC do not bind hsp60 or hsp70. Given the likely importance of the internalization of hsp70 by APC in the induction of the immune responses, the finding that hsp60 and hsp70 are internalized through the same receptor(s) may explain why microbial hsp60 represents a major T cell antigen. This may rationalize the use of microbial hsp60 to prime immune responses against microbes. The lack of hsp60/70 receptors on epidermal LC raises the crucial question as to whether absence of priming of the skin and mucosal immune systems by hsp-polypeptide complexes could account for some tissue-specific diseases. This work also points to a potential advantage of using monocyte-derived DC in human immunotherapeutic applications of hsp60/70.
authors.affiliation: INSERM, Equipe Propre 99-08, Etablissement Français du Sang-Alsace, 10 rue Spielmann, BP 36, F-67065 Strasbourg Cedex, France. dlipsker@noos.fr
authors.forename: Dan
authors.initials: D
authors.lastname: Lipsker
authors.forename: Umit
authors.initials: U
authors.lastname: Ziylan
authors.forename: Danièle
authors.initials: D
authors.lastname: Spehner
authors.forename: Fabienne
authors.initials: F
authors.lastname: Proamer
authors.forename: Huguette
authors.initials: H
authors.lastname: Bausinger
authors.forename: Pascale
authors.initials: P
authors.lastname: Jeannin
authors.forename: Jean
authors.initials: J
authors.lastname: Salamero
authors.forename: Alain
authors.initials: A
authors.lastname: Bohbot
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cazenave
authors.forename: Robert
authors.initials: R
authors.lastname: Drillien
authors.forename: Yves
authors.initials: Y
authors.lastname: Delneste
authors.forename: Daniel
authors.initials: D
authors.lastname: Hanau
authors.forename: Henri
authors.initials: H
authors.lastname: de la Salle
mesh_terms: D017951:Antigen Presentation; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation; D018834:Chaperonin 60 / Q000378:metabolism*; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D018952:Antigens, CD34; D018834:Chaperonin 60; D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors