Immunoproteasome assembly and antigen presentation in mice lacking both PA28alpha and PA28beta.

Abstract

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.

• Authors: S Murata, H Udono, N Tanahashi, N Hamada, K Watanabe, K Adachi, T Yamano, K Yui, N Kobayashi, M Kasahara, K Tanaka, T Chiba
• Journal: The EMBO journal (EMBO J) Vol. 20 Issue 21 Pg. 5898-907 (Nov 01 2001) ISSN: 0261-4189 [Print] England
• PMID: 11689430 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantigens
• Egg Proteins
• Epitopes
• Immunodominant Epitopes
• Ki antigen
• Multienzyme Complexes
• OVA-8
• Peptide Fragments
• Proteins
• RNA, Messenger
• Adenosine Triphosphate
• Ovalbumin
• Peptide Hydrolases
• Cysteine Endopeptidases
• Proteasome Endopeptidase Complex
• Psme1 protein, mouse
• Psme2 protein, mouse
• Intramolecular Oxidoreductases
• dopachrome isomerase

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Antigen Presentation (drug effects, physiology)
• Autoantigens
• Cysteine Endopeptidases (biosynthesis, immunology)
• Egg Proteins (immunology)
• Epitopes (immunology)
• Immunodominant Epitopes (immunology)
• Influenza A virus (immunology)
• Intramolecular Oxidoreductases (genetics, immunology)
• Mice
• Mice, Knockout
• Mice, Mutant Strains
• Multienzyme Complexes (biosynthesis, immunology)
• Organ Specificity (drug effects, physiology)
• Ovalbumin (immunology)
• Peptide Fragments
• Peptide Hydrolases
• Proteasome Endopeptidase Complex
• Proteins (genetics, metabolism)
• RNA, Messenger (metabolism)
• T-Lymphocytes (cytology, immunology, metabolism)
• T-Lymphocytes, Cytotoxic (cytology, immunology, metabolism)