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Science 316 (5829): 1349-1353

Copyright © 2007 by the American Association for the Advancement of Science

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

Abstract: 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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