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ReportsRegulation of CD8+ T Cell Development by Thymus-Specific Proteasomes
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 Irestricted 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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Science. ISSN 0036-8075 (print), 1095-9203 (online)