The Cytosolic Endopeptidase, Thimet Oligopeptidase, Destroys Antigenic Peptides and Limits the Extent of MHC Class I Antigen Presentation
| Autor: | Wanyong Zeng, Ian A. York, Annie X. Y. Mo, Kristen Lemerise, Kenneth L. Rock, Carmela R. Abraham, Tomo Saric, Yuelei Shen, Alfred L. Goldberg |
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| Jazyk: | angličtina |
| Předmět: |
Proteasome Endopeptidase Complex
Antigen presentation Immunology Gene Expression Endoplasmic Reticulum Mice Cytosol Multienzyme Complexes MHC class I Animals Humans Immunology and Allergy Antigens Antigen Presentation Thimet oligopeptidase biology MHC class I antigen Antigen processing Cell Membrane Histocompatibility Antigens Class I Metalloendopeptidases Transporter associated with antigen processing Endopeptidase Cysteine Endopeptidases Infectious Diseases Biochemistry COS Cells biology.protein Metalloendopeptidase Peptides HeLa Cells |
| Zdroj: | Immunity. (3):429-440 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/S1074-7613(03)00058-X |
| Popis: | Most antigenic peptides presented on MHC class I molecules are generated by proteasomes during protein breakdown. It is unknown whether these peptides are protected from destruction by cytosolic peptidases. In cytosolic extracts, most antigenic peptides are degraded by the metalloendopeptidase, thimet oligopeptidase (TOP). We therefore examined whether TOP destroys antigenic peptides in vivo. When TOP was overexpressed in cells, class I presentation of antigenic peptides was reduced. In contrast, TOP overexpression didn't reduce presentation of peptides generated in the endoplasmic reticulum or endosomes. Conversely, preventing TOP expression with siRNA enhanced presentation of antigenic peptides. TOP therefore plays an important role in vivo in degrading peptides released by proteasomes and is a significant factor limiting the extent of antigen presentation. |
| Databáze: | OpenAIRE |
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