Immunoproteasome assembly and antigen presentation in mice lacking both PA28alpha and PA28beta
Copyright policy )Immunoproteasome assembly and antigen presentation in mice lacking both PA28alpha and PA28beta
Two members of the proteasome activator, PA28alpha and PA28beta, form a heteropolymer that binds to both ends of the 20S proteasome. Evidence in vitro indicates that this interferon-gamma (IFN-gamma)-inducible heteropolymer is involved in the processing of intracellular antigens, but its functions in vivo remain elusive. To investigate the role of PA28alpha/beta in vivo, we generated mice deficient in both PA28alpha and PA28beta genes. The ATP-dependent proteolytic activities were decreased in PA28alpha(-/-)/beta(-/-) cells, suggesting that 'hybrid proteasomes' are involved in protein degradation. Treatment of PA28alpha(-/-)/beta(-/-) cells with IFN-gamma resulted in sufficient induction of the 'immunoproteasome'. Moreover, splenocytes from PA28alpha(-/-)/beta(-/-) mice displayed no apparent defects in processing of ovalbumin. These results are in marked contrast to the previous finding that immunoproteasome assembly and immune responses were impaired in PA28beta(-/-) mice. PA28alpha(-/-)/beta(-/-) mice also showed apparently normal immune responses against infection with influenza A virus. However, they almost completely lost the ability to process a melanoma antigen TRP2-derived peptide. Hence, PA28alpha/beta is not a prerequisite for antigen presentation in general, but plays an essential role for the processing of certain antigens.
- Nagasaki University Japan
- Medical Research Council United Kingdom
- Tokyo Metropolitan Institute of Medical Science Japan
- The Graduate University for Advanced Studies, SOKENDAI Japan
- MRC Laboratory of Molecular Biology United Kingdom
Mice, Knockout, Antigen Presentation, Proteasome Endopeptidase Complex, Immunodominant Epitopes, Ovalbumin, Egg Proteins, Proteins, Autoantigens, Mice, Mutant Strains, Peptide Fragments, Intramolecular Oxidoreductases, Cysteine Endopeptidases, Epitopes, Mice, Adenosine Triphosphate, Influenza A virus, Multienzyme Complexes, Organ Specificity, Animals, Peptide Hydrolases
Mice, Knockout, Antigen Presentation, Proteasome Endopeptidase Complex, Immunodominant Epitopes, Ovalbumin, Egg Proteins, Proteins, Autoantigens, Mice, Mutant Strains, Peptide Fragments, Intramolecular Oxidoreductases, Cysteine Endopeptidases, Epitopes, Mice, Adenosine Triphosphate, Influenza A virus, Multienzyme Complexes, Organ Specificity, Animals, Peptide Hydrolases
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