Impaired immunoproteasome assembly and immune responses in PA28(-/-) mice

Tobias Preckel, Wai Ping Fung-Leung, Zeling Cai, Antonella Vitiello, Luisa Salter-Cid, Ola Winqvist, Tom G. Wolfe, Matthias Von Herrath, Ana Angulo, Peter Ghazal, Jiing Dwan Lee, Anne M. Fourie, Ying Wu, Jesse Pang, Karen Ngo, Per A. Peterson, Klaus Früh, Young Yang

Research output: Contribution to journalArticle

143 Scopus citations

Abstract

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 in PA28(-/-) 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.

Original languageEnglish (US)
Pages (from-to)2162-2165
Number of pages4
JournalScience
Volume286
Issue number5447
DOIs
StatePublished - Dec 10 1999

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    Preckel, T., Fung-Leung, W. P., Cai, Z., Vitiello, A., Salter-Cid, L., Winqvist, O., Wolfe, T. G., Von Herrath, M., Angulo, A., Ghazal, P., Lee, J. D., Fourie, A. M., Wu, Y., Pang, J., Ngo, K., Peterson, P. A., Früh, K., & Yang, Y. (1999). Impaired immunoproteasome assembly and immune responses in PA28(-/-) mice. Science, 286(5447), 2162-2165. https://doi.org/10.1126/science.286.5447.2162