Abstract
The surface presentation of peptides by major histocompatibility complex (MHC) class I molecules is critical to CD8(+) T cell-mediated adaptive immune responses. Aminopeptidases have been linked to the editing of peptides for MHC class I loading, but carboxy-terminal editing is thought to be due to proteasome cleavage. By analysis of wild-type mice and mice genetically deficient in or overexpressing the dipeptidase angiotensin-converting enzyme (ACE), we have now identified ACE as having a physiological role in the processing of peptides for MHC class I. ACE edited the carboxyl terminus of proteasome-produced MHC class I peptides. The lack of ACE exposed new antigens but also abrogated some self antigens. ACE had substantial effects on the surface expression of MHC class I in a haplotype-dependent manner. We propose a revised model of peptide processing for MHC class I by introducing carboxypeptidase activity into the process.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adaptive Immunity
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Animals
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Antigen Presentation / genetics
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Autoantigens / immunology
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Autoantigens / metabolism
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Cells, Cultured
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Clonal Selection, Antigen-Mediated* / genetics
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Gene Expression Regulation / genetics
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Gene Expression Regulation / immunology
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Histocompatibility Antigens Class I / genetics
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Histocompatibility Antigens Class I / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Peptidyl-Dipeptidase A / genetics
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Peptidyl-Dipeptidase A / immunology
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Peptidyl-Dipeptidase A / metabolism*
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Proteasome Endopeptidase Complex / metabolism*
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Protein Binding / immunology
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T-Cell Antigen Receptor Specificity / genetics
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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Transgenes / genetics
Substances
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Autoantigens
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Histocompatibility Antigens Class I
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Peptide Fragments
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Peptidyl-Dipeptidase A
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Proteasome Endopeptidase Complex