Abstract
The studies reported here bear on the events in the cytosol that lead to trafficking of peptides during antigen processing and presentation by major histocompatibility complex (MHC) I molecules. We have introduced free antigenic peptides or antigenic peptides bound to serum albumin or to cytosolic heat shock proteins hsp90 (and its endoplasmic reticular homologue gp96) or hsp70 into the cytosol of living cells and have monitored the presentation of the peptides by appropriate MHC I molecules. The experiments show that (i) free peptides or serum albumin-bound peptides, introduced into the cytosol, become ligands of MHC I molecules at a far lower efficiency than peptides chaperoned by any of the heat shock proteins tested and (ii) treatment of cells with deoxyspergualin, a drug that binds hsp70 and hsp90 with apparent specificity, abrogates the ability of cells to present antigenic peptides through MHC I molecules, and introduction of additional hsp70 into the cytosol overcomes this abrogation. These results suggest for the first time a functional role for cytosolic chaperones in antigen processing.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antigens / metabolism*
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Antigens, Neoplasm / metabolism*
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Cell Line
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Cysteine Endopeptidases / metabolism
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Cytosol / immunology
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Cytosol / metabolism
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Cytotoxicity, Immunologic*
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Epitopes / chemistry
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Epitopes / immunology
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Fatty Acids, Monounsaturated
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Fluorescent Dyes
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Guanidines / pharmacology
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HSP70 Heat-Shock Proteins / metabolism*
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HSP90 Heat-Shock Proteins / metabolism*
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Histocompatibility Antigens Class I / immunology*
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Immunosuppressive Agents / pharmacology
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Kinetics
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Ligands
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Major Histocompatibility Complex
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Molecular Sequence Data
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Multienzyme Complexes / metabolism
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Peptide Fragments / chemical synthesis
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Peptide Fragments / immunology
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Protease Inhibitors / pharmacology
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Proteasome Endopeptidase Complex
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Protein Transport
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Quaternary Ammonium Compounds
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T-Lymphocytes, Cytotoxic / immunology*
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Transfection
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Tumor Cells, Cultured
Substances
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Antigens
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Antigens, Neoplasm
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Epitopes
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Fatty Acids, Monounsaturated
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Fluorescent Dyes
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Guanidines
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HSP70 Heat-Shock Proteins
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HSP90 Heat-Shock Proteins
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Histocompatibility Antigens Class I
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Immunosuppressive Agents
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Ligands
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Multienzyme Complexes
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Peptide Fragments
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Protease Inhibitors
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Quaternary Ammonium Compounds
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sarcoma glycoprotein gp96 rejection antigens
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex
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1,2-dioleoyloxy-3-(trimethylammonium)propane
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gusperimus