Immunoproteasome assembly and antigen presentation in mice lacking both PA28 alpha and PA28 beta

Citation
S. Murata et al., Immunoproteasome assembly and antigen presentation in mice lacking both PA28 alpha and PA28 beta, EMBO J, 20(21), 2001, pp. 5898-5907
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
EMBO JOURNAL
ISSN journal
0261-4189 → ACNP
Volume
20
Issue
21
Year of publication
2001
Pages
5898 - 5907
Database
ISI
SICI code
0261-4189(20011101)20:21<5898:IAAAPI>2.0.ZU;2-D
Abstract
Two members of the proteasome activator, PA28 alpha and PA28 beta, form a h eteropolymer that binds to both ends of the 20S proteasome. Evidence in vit ro 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 PA28 alpha/beta in vivo , we generated mice deficient in both PA28 alpha and PA28 beta genes. The A TP-dependent proteolytic activities were decreased in PA28 alpha (-/-)/beta (-/-) cells, suggesting that 'hybrid proteasomes' are involved in protein degradation. Treatment of PA28 alpha (-/-)/beta (-/-) cells with IFN-gamma resulted in sufficient induction of the 'immunoproteasome'. Moreover, splen ocytes from PA28 alpha (-/-)/beta (-/-) mice displayed no apparent defects in processing of ovalbumin. These results are in marked contrast to the pre vious finding that immunoproteasome assembly and immune responses were impa ired in PA28 beta (-/-) mice. PA28 alpha (-/-)/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 an tigen TRP2-derived peptide. Hence, PA28 alpha/beta is not a prerequisite fo r antigen presentation in general, but plays an essential role for the proc essing of certain antigens.