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 journalArticle

119 Citations (Scopus)

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-/--/- cells, suggesting that 'hybrid proteasomes' are involved in protein degradation. Treatment of PA28α-/--/- cells with IFN-γ resulted in sufficient induction of the 'immunoproteasome'. Moreover, splenocytes from PA28α-/--/- 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-/--/- 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 languageEnglish
Pages (from-to)5898-5907
Number of pages10
JournalEMBO Journal
Volume20
Issue number21
DOIs
Publication statusPublished - Nov 1 2001
Externally publishedYes

Keywords

  • Antigen processing
  • Gene targeting
  • Immunoproteasome
  • PA28α/PA28β

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Murata, S., Udono, H., Tanahashi, N., Hamada, N., Watanabe, K., Adachi, K., Yamano, T., Yui, K., Kobayashi, N., Kasahara, M., Tanaka, K., & Chiba, T. (2001). Immunoproteasome assembly and antigen presentation in mice lacking both PA28α and PA28β. EMBO Journal, 20(21), 5898-5907. https://doi.org/10.1093/emboj/20.21.5898