Abstract
Immunoproteasome subunits low-molecular mass polypeptide (LMP)2 and LMP7 affect Ag presentation by MHC class I molecules. In the present study, we investigated the function of the third immunosubunit LMP10/multicatalytic endopeptidase complex-like (MECL)-1 (beta2i) in MECL-1 gene-targeted mice. The number of CD8+ splenocytes in MECL-1-/- mice was 20% lower than in wild-type mice. Infection with lymphocytic choriomeningitis virus (LCMV) elicited a markedly reduced cytotoxic T cell (CTL) response to the LCMV epitopes GP276-286/Db and NP205-212/Kb in MECL-1-/- mice. The weak CTL response to GP276-286/Db was not due to an impaired generation of this epitope but was attributed to a decreased precursor frequency of GP276-286/Db-specific T cells. The expansion of TCR-Vbeta10+ T cells, which contain GP276-286/Db-specific cells, was reduced in LCMV-infected MECL-1-/- mice. Taken together, our data reveal an in vivo function of MECL-1 in codetermining the T cell repertoire for an antiviral CTL response.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Antigen Presentation / genetics
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Arenaviridae Infections / enzymology
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Arenaviridae Infections / genetics
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Arenaviridae Infections / immunology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / pathology
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CD8-Positive T-Lymphocytes / virology
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Caspases / metabolism
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Cell Line
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Cysteine Endopeptidases / deficiency*
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Cysteine Endopeptidases / genetics*
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Cysteine Endopeptidases / metabolism
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Cysteine Endopeptidases / physiology
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Cytotoxicity, Immunologic / genetics
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Gene Targeting
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Humans
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Immunodominant Epitopes / immunology
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Liver / enzymology
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Liver / virology
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Lymphocytic choriomeningitis virus / immunology
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Lymphopenia / enzymology
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Lymphopenia / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Proteasome Endopeptidase Complex / genetics
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Proteasome Endopeptidase Complex / metabolism
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Proteasome Inhibitors
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T-Lymphocyte Subsets / enzymology*
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / transplantation
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / pathology
Substances
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Immunodominant Epitopes
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Proteasome Inhibitors
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LMP-2 protein
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Caspases
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex
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Psmb10 protein, mouse