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Immunoproteasome assembly and antigen presentation in mice lacking both PA28α and PA28β
Author(s) -
Murata Shigeo,
Udono Heiichiro,
Tanahashi Nobuyuki,
Hamada Nobuyuki,
Watanabe Ken,
Adachi Kei,
Yamano Taketoshi,
Yui Katsuyuki,
Kobayashi Nobuyuki,
Kasahara Masanori,
Tanaka Keiji,
Chiba Tomoki
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.21.5898
Subject(s) - biology , antigen processing , antigen , antigen presentation , proteasome , immune system , ovalbumin , proteolysis , in vivo , microbiology and biotechnology , interferon gamma , immunology , t cell , biochemistry , enzyme , genetics
Two members of the proteasome activator, PA28α and PA28β, form a heteropolymer that binds to both ends of the 20S proteasome. Evidence in vitro indicates that this interferon‐γ (IFN‐γ)‐inducible heteropolymer is involved in the processing of intracellular antigens, but its functions in vivo remain elusive. To investigate the role of PA28α/β in vivo , we generated mice deficient in both PA28α and PA28β genes. The ATP‐dependent proteolytic activities were decreased in PA28α −/− /β −/− cells, suggesting that ‘hybrid proteasomes’ are involved in protein degradation. Treatment of PA28α −/− /β −/− cells with IFN‐γ resulted in sufficient induction of the ‘immunoproteasome’. Moreover, splenocytes from PA28α −/− /β −/− 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 PA28β −/− mice. PA28α −/− /β −/− 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, PA28α/β is not a prerequisite for antigen presentation in general, but plays an essential role for the processing of certain antigens.