Abstract
Proteasomes are responsible for generating peptides presented by the class I major histocompatibility complex (MHC) molecules of the immune system. Here, we report the identification of a previously unrecognized catalytic subunit called beta5t. beta5t is expressed exclusively in cortical thymic epithelial cells, which are responsible for the positive selection of developing thymocytes. Although the chymotrypsin-like activity of proteasomes is considered to be important for the production of peptides with high affinities for MHC class I clefts, incorporation of beta5t into proteasomes in place of beta5 or beta5i selectively reduces this activity. We also found that beta5t-deficient mice displayed defective development of CD8(+) T cells in the thymus. Our results suggest a key role for beta5t in generating the MHC class I-restricted CD8(+) T cell repertoire during thymic selection.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Autoantigens / immunology
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Autoantigens / metabolism
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology*
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Catalytic Domain
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Epithelial Cells / enzymology
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Histocompatibility Antigens Class I / immunology
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Histocompatibility Antigens Class I / metabolism
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Humans
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Lymphopoiesis
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Molecular Sequence Data
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Peptides / chemistry
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Peptides / metabolism
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Proteasome Endopeptidase Complex / chemistry
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Proteasome Endopeptidase Complex / genetics
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Proteasome Endopeptidase Complex / metabolism*
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Spleen / cytology
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Spleen / immunology
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology
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Thymus Gland / cytology*
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Thymus Gland / enzymology*
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Thymus Gland / immunology
Substances
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Autoantigens
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Histocompatibility Antigens Class I
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Peptides
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Green Fluorescent Proteins
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PSMB11 protein, human
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Proteasome Endopeptidase Complex
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proteasome subunit beta5t, mouse
Associated data
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GENBANK/AB299436
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GENBANK/AB299437