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Science 1 June 2007:
Vol. 316. no. 5829, pp. 1349 - 1353
DOI: 10.1126/science.1141915
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Reports

Regulation of CD8+ T Cell Development by Thymus-Specific Proteasomes

Shigeo Murata,1,2* Katsuhiro Sasaki,1 Toshihiko Kishimoto,3,4 Shin-ichiro Niwa,5 Hidemi Hayashi,3,5 Yousuke Takahama,6 Keiji Tanaka1

Proteasomes are responsible for generating peptides presented by the class I major histocompatibility complex (MHC) molecules of the immune system. Here, we report the identification of a previously unrecognized catalytic subunit called ß5t. ß5t is expressed exclusively in cortical thymic epithelial cells, which are responsible for the positive selection of developing thymocytes. Although the chymotrypsin-like activity of proteasomes is considered to be important for the production of peptides with high affinities for MHC class I clefts, incorporation of ß5t into proteasomes in place of ß5 or ß5i selectively reduces this activity. We also found that ß5t-deficient mice displayed defective development of CD8+ T cells in the thymus. Our results suggest a key role for ß5t in generating the MHC class I–restricted CD8+ T cell repertoire during thymic selection.

1 Laboratory of Frontier Science, Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan.
2 Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan.
3 Proteome Analysis Center, Faculty of Science, Toho University, Funabashi, Chiba 274-8510, Japan.
4 Department of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba 274-8510, Japan.
5 Link Genomics, Chuo-ku, Tokyo 103-0024, Japan.
6 Division of Experimental Immunology, Institute for Genome Research, Graduate School of Medical Science, University of Tokushima, Tokushima 770-8503, Japan.

* To whom correspondence should be addressed. E-mail: smurata{at}rinshoken.or.jp

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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U. Tomaru, A. Ishizu, S. Murata, Y. Miyatake, S. Suzuki, S. Takahashi, T. Kazamaki, J. Ohara, T. Baba, S. Iwasaki, et al. (2009)
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Checkpoints in the Development of Thymic Cortical Epithelial Cells.
S. Shakib, G. E. Desanti, W. E. Jenkinson, S. M. Parnell, E. J. Jenkinson, and G. Anderson (2009)
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The Proteasome Immunosubunit Multicatalytic Endopeptidase Complex-Like 1 Is a T-Cell-Intrinsic Factor Influencing Homeostatic Expansion.
D. M. W. Zaiss, N. de Graaf, and A. J. A. M. Sijts (2008)
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Why T Cells of Thymic Versus Extrathymic Origin Are Functionally Different.
M.-E. Blais, S. Brochu, M. Giroux, M.-P. Belanger, G. Dulude, R.-P. Sekaly, and C. Perreault (2008)
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Science. ISSN 0036-8075 (print), 1095-9203 (online)