Abstract
Many viral proteins that contain MHC class I-restricted peptides are long-lived, and it is elusive how they can give rise to class I epitopes. Recently, we showed that direct presentation of an epitope of the long-lived lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP) required neosynthesis in accordance with the defective ribosomal products hypothesis. In this study, we report that LCMV-NP can be cross-primed in mice using either LCMV-NP-transfected human HEK293 or BALB/c-derived B8 cells as Ag donor cells. In addition, we establish that contrary to direct presentation, cross-presentation required accumulation of the mature LCMV-NP and could not be sustained by the newly synthesized LCMV-NP protein, intermediate proteasomal degradation products, or the minimal NP396 epitope. Nevertheless, NP cross-presentation was enhanced by heat shock and was blunted by inhibitors of heat shock protein 90 and gp96. We propose that cross-presentation has evolved to sustain the presentation of stable viral proteins when their neosynthesis has ceased in infected donor cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / antagonists & inhibitors
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Adjuvants, Immunologic / physiology*
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Animals
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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Antigens, Neoplasm / metabolism
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Antigens, Neoplasm / physiology
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Cell Death / immunology
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Cell Death / radiation effects
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Cell Line
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Cross-Priming / immunology*
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Female
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HSP90 Heat-Shock Proteins / antagonists & inhibitors
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HSP90 Heat-Shock Proteins / physiology*
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Heat-Shock Response / immunology
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Humans
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Lymphocytic choriomeningitis virus / immunology*
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Mediator Complex
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Nuclear Proteins / immunology
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Nuclear Proteins / metabolism
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Nucleoproteins / biosynthesis*
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Nucleoproteins / genetics
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Nucleoproteins / immunology*
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Nucleoproteins / metabolism
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Peptide Fragments / biosynthesis*
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Peptide Fragments / genetics
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Peptide Fragments / immunology*
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Peptide Fragments / metabolism
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Proteasome Endopeptidase Complex / immunology
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Proteasome Endopeptidase Complex / metabolism
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Protein Processing, Post-Translational / immunology
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Ribosomal Proteins / antagonists & inhibitors
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Ribosomal Proteins / biosynthesis
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Ribosomal Proteins / physiology
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Trans-Activators / immunology
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Trans-Activators / metabolism
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Transfection
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Ultraviolet Rays
Substances
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Adjuvants, Immunologic
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Antigens, Neoplasm
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DRIP, VDR interacting protein complex
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HSP90 Heat-Shock Proteins
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Mediator Complex
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Nuclear Proteins
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Nucleoproteins
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Peptide Fragments
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Ribosomal Proteins
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Trans-Activators
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nucleoprotein peptide 394-408, lymphocytic choriomeningitis virus
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sarcoma glycoprotein gp96 rejection antigens
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Proteasome Endopeptidase Complex