The role of the proteasome in the generation of MHC class I ligands and immune responses |
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Authors: | E?J?A?M?Sijts Email author" target="_blank">P-M?KloetzelEmail author |
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Institution: | 1.Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine,Utrecht University,Utrecht,The Netherlands;2.Institut für Biochemie,Charité-Universit?tsmedizin Berlin,Berlin,Germany |
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Abstract: | The ubiquitin–proteasome system (UPS) degrades intracellular proteins into peptide fragments that can be presented by major
histocompatibility complex (MHC) class I molecules. While the UPS is functional in all mammalian cells, its subunit composition
differs depending on cell type and stimuli received. Thus, cells of the hematopoietic lineage and cells exposed to (pro)inflammatory
cytokines express three proteasome immunosubunits, which form the catalytic centers of immunoproteasomes, and the proteasome
activator PA28. Cortical thymic epithelial cells express a thymus-specific proteasome subunit that induces the assembly of
thymoproteasomes. We here review new developments regarding the role of these different proteasome components in MHC class
I antigen processing, T cell repertoire selection and CD8 T cell responses. We further discuss recently discovered functions
of proteasomes in peptide splicing, lymphocyte survival and the regulation of cytokine production and inflammatory responses. |
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