Abstract
An important mammalian defence strategy against intracellular pathogens is the presentation of cytoplasmically derived short peptides by major histocompatibility complex (MHC) class I molecules to cytotoxic T lymphocytes. MHC class I molecules assemble in the endoplasmic reticulum (ER) with chaperones, including calnexin and calreticulin, before binding to the transporter associated with antigen processing (TAP). We show here that the thiol-dependent reductase ERp57 (also known as ER60 protease) is involved in MHC class I assembly. ERp57 co-purified with the rat TAP complex (comprising TAP1 and TAP2), and associated with MHC class I molecules at an early stage in their biosynthesis. This association was sensitive to castanospermine, which inhibits the processing of glycoproteins. Human MHC class I molecules were also found to associate with ERp57. We conclude that ERp57 is a newly identified component of the MHC class I pathway, and that it appears to interact with MHC class I molecules before they associate with TAP.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 2
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ATP Binding Cassette Transporter, Subfamily B, Member 3
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ATP-Binding Cassette Transporters / metabolism
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Amino Acid Sequence
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Animals
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Antigen Presentation*
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Cell Line
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Endoplasmic Reticulum / metabolism*
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Heat-Shock Proteins / metabolism
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Heat-Shock Proteins / physiology*
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Histocompatibility Antigens Class I / metabolism*
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Humans
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Isomerases / metabolism
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Isomerases / physiology*
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Molecular Sequence Data
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Protein Disulfide Reductase (Glutathione) / metabolism
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Protein Disulfide Reductase (Glutathione) / physiology*
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Protein Disulfide-Isomerases
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Rats
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Tumor Cells, Cultured
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 2
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ATP Binding Cassette Transporter, Subfamily B, Member 3
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ATP-Binding Cassette Transporters
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Heat-Shock Proteins
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Histocompatibility Antigens Class I
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TAP1 protein, human
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Tap1 protein, rat
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Tap2 protein, rat
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TAP2 protein, human
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Protein Disulfide Reductase (Glutathione)
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Isomerases
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PDIA3 protein, rat
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Protein Disulfide-Isomerases
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PDIA3 protein, human