Abstract
Effective MHC class I peptide loading requires the proteolytic degradation of cytosolic proteins and the TAP-mediated translocation of peptides across the membrane of the endoplasmic reticulum. The proteasome is emerging as the main cytosolic protease generating class I binding peptides. The recent elucidation of the proteasome crystal structure, together with the use of functional inhibitors, has enhanced our understanding of proteasome function. Genetic analysis of a novel mutant cell line emphasizes the importance of the TAP-class I interaction in the assembly of mature class I heterotrimers, and suggests that additional MHC-encoded components are required.
Publication types
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Research Support, Non-U.S. Gov't
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Review
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 / genetics
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ATP-Binding Cassette Transporters / immunology
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ATP-Binding Cassette Transporters / metabolism
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Animals
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Antigen Presentation*
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Cysteine Endopeptidases / chemistry
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Cysteine Endopeptidases / metabolism
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Cysteine Endopeptidases / physiology
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Cytotoxicity, Immunologic
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Endoplasmic Reticulum / metabolism
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Epitopes / immunology
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Epitopes / metabolism
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Histocompatibility Antigens Class I / chemistry
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Histocompatibility Antigens Class I / metabolism*
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Humans
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Interferon-gamma / immunology
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Interferon-gamma / metabolism
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Mice
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Mice, Knockout
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Models, Molecular
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Multienzyme Complexes / chemistry
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Multienzyme Complexes / metabolism
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Multienzyme Complexes / physiology
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Proteasome Endopeptidase Complex
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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Epitopes
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Histocompatibility Antigens Class I
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Multienzyme Complexes
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TAP1 protein, human
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Tap1 protein, mouse
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Tap2 protein, mouse
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TAP2 protein, human
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Interferon-gamma
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex