Immunoproteasome assembly and antigen presentation in mice lacking both PA28α and PA28β

Shigeo Murata; Heiichiro Udono; Nobuyuki Tanahashi; Nobuyuki Hamada; Ken Watanabe; Kei Adachi; Taketoshi Yamano; Katsuyuki Yui; Nobuyuki Kobayashi; Masanori Kasahara; Keiji Tanaka; Tomoki Chiba

doi:10.1093/emboj/20.21.5898

Immunoproteasome assembly and antigen presentation in mice lacking both PA28α and PA28β

Shigeo Murata, Heiichiro Udono, Nobuyuki Tanahashi, Nobuyuki Hamada, Ken Watanabe, Kei Adachi, Taketoshi Yamano, Katsuyuki Yui, Nobuyuki Kobayashi, Masanori Kasahara, Keiji Tanaka, Tomoki Chiba

Research output: Contribution to journal › Article › peer-review

141 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	5898-5907
Number of pages	10
Journal	EMBO Journal
Volume	20
Issue number	21
DOIs	https://doi.org/10.1093/emboj/20.21.5898
State	Published - Nov 1 2001
Externally published	Yes

Keywords

Antigen processing
Gene targeting
Immunoproteasome
PA28α/PA28β

ASJC Scopus subject areas

General Neuroscience
Molecular Biology
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

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10.1093/emboj/20.21.5898

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title = "Immunoproteasome assembly and antigen presentation in mice lacking both PA28α and PA28β",

abstract = "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.",

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author = "Shigeo Murata and Heiichiro Udono and Nobuyuki Tanahashi and Nobuyuki Hamada and Ken Watanabe and Kei Adachi and Taketoshi Yamano and Katsuyuki Yui and Nobuyuki Kobayashi and Masanori Kasahara and Keiji Tanaka and Tomoki Chiba",

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T1 - Immunoproteasome assembly and antigen presentation in mice lacking both PA28α and PA28β

AU - Murata, Shigeo

AU - Udono, Heiichiro

AU - Tanahashi, Nobuyuki

AU - Hamada, Nobuyuki

AU - Watanabe, Ken

AU - Adachi, Kei

AU - Yamano, Taketoshi

AU - Yui, Katsuyuki

AU - Kobayashi, Nobuyuki

AU - Kasahara, Masanori

AU - Tanaka, Keiji

AU - Chiba, Tomoki

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N2 - 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.

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KW - Gene targeting

KW - Immunoproteasome

KW - PA28α/PA28β

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Immunoproteasome assembly and antigen presentation in mice lacking both PA28α and PA28β

Abstract

Keywords

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