Impaired Immunoproteasome Assembly and Immune Responses in PA28 −/− Mice
- 10 December 1999
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 286 (5447) , 2162-2165
- https://doi.org/10.1126/science.286.5447.2162
Abstract
In vitro PA28 binds and activates proteasomes. It is shown here that mice with a disrupted PA28b gene lack PA28a and PA28b polypeptides, demonstrating that PA28 functions as a hetero-oligomer in vivo. Processing of antigenic epitopes derived from exogenous or endogenous antigens is altered inPA28–/– mice. Cytotoxic T lymphocyte responses are impaired, and assembly of immunoproteasomes is greatly inhibited in mice lacking PA28. These results show that PA28 is necessary for immunoproteasome assembly and is required for efficient antigen processing, thus demonstrating the importance of PA28-mediated proteasome function in immune responses.Keywords
This publication has 21 references indexed in Scilit:
- DEGRADATION OF CELL PROTEINS AND THE GENERATION OF MHC CLASS I-PRESENTED PEPTIDESAnnual Review of Immunology, 1999
- Conformational Changes in the 20S Proteasome upon Macromolecular Ligand Binding Analyzed with Monoclonal AntibodiesArchives of Biochemistry and Biophysics, 1999
- Relative Functions of the α and β Subunits of the Proteasome Activator, PA28Journal of Biological Chemistry, 1997
- Comparison of cytotoxic T lymphocyte responses induced by peptide or DNA immunization: Implications on immunogenicity and immunodominanceEuropean Journal of Immunology, 1997
- Coordinated Dual Cleavages Induced by the Proteasome Regulator PA28 Lead to Dominant MHC LigandsCell, 1996
- A role for the proteasome regulator PA28α in antigen presentationNature, 1996
- Clone-specific T cell receptor antagonists of major histocompatibility complex class I-restricted cytotoxic T cells.The Journal of Experimental Medicine, 1993
- Introduction of soluble protein into the class I pathway of antigen processing and presentationCell, 1988
- T-cell-specific deletion of T-cell receptor transgenes allows functional rearrangement of endogenous α- and β-genesNature, 1988
- Anaphylaxis in Mast Cell-Deficient MiceJournal of Investigative Dermatology, 1984