Thimet Oligopeptidase (EC 3.4.24.15), a Novel Protein on the Route of MHC Class I Antigen Presentation

The initial processing of antigens leading to major histocompatibility complex (MHC) class I antigenic peptides is carried out by the proteasome. However, how the final epitopes are generated and protected from degradation by cytosolic peptidases remains unknown. Coincidentally, peptides associated...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1999-02, Vol.255 (3), p.591-595
Main Authors: Silva, Celio L., Portaro, Fernanda C.V., Bonato, Vânia L.D., de Camargo, Antonio C.M., Ferro, Emer S.
Format: Article
Language:English
Subjects:
antigen presentation
Antigen-Presenting Cells - enzymology
Antigen-Presenting Cells - immunology
CD4-Positive T-Lymphocytes - enzymology
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - enzymology
CD8-Positive T-Lymphocytes - immunology
Cysteine Endopeptidases - metabolism
Cytotoxicity Tests, Immunologic
Enzyme Inhibitors
Flow Cytometry
Histocompatibility Antigens Class I - immunology
Immunohistochemistry
Liposomes - metabolism
Macrophages, Peritoneal - metabolism
Metalloendopeptidases - immunology
MHC class I
Multienzyme Complexes - metabolism
Oligopeptides - pharmacology
peptidase
Proteasome Endopeptidase Complex
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Summary:The initial processing of antigens leading to major histocompatibility complex (MHC) class I antigenic peptides is carried out by the proteasome. However, how the final epitopes are generated and protected from degradation by cytosolic peptidases remains unknown. Coincidentally, peptides associated with the MHC class I molecules range from 8 to 13 amino acid residues, similarly to the optimum substrate size required for the cytosolic thimet oligopeptidase. Here we have investigated the putative intracellular function of thimet oligopeptidase related to antigen presentation. Using a well-characterized antigen-presenting cell system, we were able to demonstrate either inhibition or stimulation of CD8 T cell proliferation and cytotoxicity, manipulating intracellular thimet oligopeptidase levels with its specific inhibitor cFP-Ala-Ala-Tyr-pAb or loading the enzyme itself into the antigen-presenting cells. Our results suggest that thimet oligopeptidase should take an important function in the pathway of antigen presentation via MHC class I through a mechanism yet unknown.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1999.0250