Impaired Immunoproteasome Assembly and Immune Responses in PA28−/− Mice

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Science  10 Dec 1999:
Vol. 286, Issue 5447, pp. 2162-2165
DOI: 10.1126/science.286.5447.2162

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In vitro PA28 binds and activates proteasomes. It is shown here that mice with a disrupted PA28b gene lack PA28a and PA28b polypeptides, demonstrating that PA28 functions as a hetero-oligomer in vivo. Processing of antigenic epitopes derived from exogenous or endogenous antigens is altered inPA28–/– mice. Cytotoxic T lymphocyte responses are impaired, and assembly of immunoproteasomes is greatly inhibited in mice lacking PA28. These results show that PA28 is necessary for immunoproteasome assembly and is required for efficient antigen processing, thus demonstrating the importance of PA28-mediated proteasome function in immune responses.

  • * Present address: Agilent Technologies Deutschland GmbH, Hewlett Packard Strasse 8, 76337 Waldbronn, Germany.

  • Present address: University Hospital of Uppsala, Uppsala S-751 85, Sweden.

  • To whom correspondence should be addressed. E-mail: kfrueh{at} (K.F.) or yyang{at}

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