title: Bacterial heat shock proteins promote CD91-dependent class I MHC cross-presentation of chaperoned peptide to CD8+ T cells by cytosolic mechanisms in dendritic cells versus vacuolar mechanisms in macrophages.
abstract: APCs process mammalian heat shock protein (HSP):peptide complexes to present HSP-chaperoned peptides on class I MHC (MHC-I) molecules to CD8(+) T cells. HSPs are also expressed in prokaryotes and chaperone microbial peptides, but the ability of prokaryotic HSPs to contribute chaperoned peptides for Ag presentation is unknown. Our studies revealed that exogenous bacterial HSPs (Escherichia coli DnaK and Mycobacterium tuberculosis HSP70) delivered an extended OVA peptide for processing and MHC-I presentation by both murine macrophages and dendritic cells. HSP-enhanced MHC-I peptide presentation occurred only if peptide was complexed to the prokaryotic HSP and was dependent on CD91, establishing CD91 as a receptor for prokaryotic as well as mammalian HSPs. Inhibition of cytosolic processing mechanisms (e.g., by transporter for Ag presentation deficiency or brefeldin A) blocked HSP-enhanced peptide presentation in dendritic cells but not macrophages. Thus, prokaryotic HSPs deliver chaperoned peptide for alternate MHC-I Ag processing and cross-presentation via cytosolic mechanisms in dendritic cells and vacuolar mechanisms in macrophages. Prokaryotic HSPs are a potential source of microbial peptide Ags during phagocytic processing of bacteria during infection and could potentially be incorporated in vaccines to enhance presentation of peptides to CD8(+) T cells.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Aaron A R
authors.initials: AA
authors.lastname: Tobian
authors.forename: David H
authors.initials: DH
authors.lastname: Canaday
authors.forename: W Henry
authors.initials: WH
authors.lastname: Boom
authors.forename: Clifford V
authors.initials: CV
authors.lastname: Harding
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D001426:Bacterial Proteins; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004527:Egg Proteins / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000502:physiology*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000502:physiology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments; D015398:Signal Transduction / Q000276:immunology; D014617:Vacuoles / Q000276:immunology / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D001426:Bacterial Proteins; D004527:Egg Proteins; D018984:Epitopes, T-Lymphocyte; D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; C444642:HSP70 protein, Mycobacterium tuberculosis; D015395:Histocompatibility Antigens Class I; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C110366:OVA-8; D010446:Peptide Fragments; D000511:alpha-Macroglobulins; D010047:Ovalbumin; C063842:dnaK protein, E coli