Abstract
Newly assembled major histocompatibility complex (MHC) class I molecules, together with the endoplasmic reticulum chaperone calreticulin, interact with the transporter associated with antigen processing (TAP) through a molecule called tapasin. The molecular cloning of tapasin revealed it to be a transmembrane glycoprotein encoded by an MHC-linked gene. It is a member of the immunoglobulin superfamily with a probable cytoplasmic endoplasmic reticulum retention signal. Up to four MHC class I-tapasin complexes were found to bind to each TAP molecule. Expression of tapasin in a negative mutant human cell line (220) restored class I-TAP association and normal class I cell surface expression. Tapasin expression also corrected the defective recognition of virus-infected 220 cells by class I-restricted cytotoxic T cells, establishing a critical functional role for tapasin in MHC class I-restricted 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, P.H.S.
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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Antigen Presentation
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Antiporters / chemistry
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Antiporters / genetics
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Antiporters / metabolism*
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Calcium-Binding Proteins / metabolism
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Calreticulin
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Cell Line
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Cell Line, Transformed
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Chromosome Mapping
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Chromosomes, Human, Pair 6
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Cloning, Molecular
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Dimerization
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Endoplasmic Reticulum / metabolism
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Genetic Linkage
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HLA Antigens / metabolism*
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Histocompatibility Antigens Class I / metabolism*
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Humans
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Immunoglobulin G / chemistry
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Immunoglobulins / chemistry
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Immunoglobulins / genetics
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Immunoglobulins / metabolism*
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Major Histocompatibility Complex / genetics
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Membrane Transport Proteins
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Molecular Sequence Data
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Ribonucleoproteins / metabolism
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Sequence Homology, Amino Acid
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T-Lymphocytes, Cytotoxic
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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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Antiporters
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Calcium-Binding Proteins
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Calreticulin
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HLA Antigens
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Histocompatibility Antigens Class I
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Immunoglobulin G
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Immunoglobulins
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Membrane Transport Proteins
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Ribonucleoproteins
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TAP1 protein, human
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tapasin
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TAP2 protein, human