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

2007/05/31 by Shigeo Murata, Katsuhiro Sasaki, Toshihiko Kishimoto +4 · 570 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Biology #CD8 #Cell biology #Cytotoxic T cell #Gene #Genetics #Immune system #Immunology #Immunotherapy and Immune Responses #In vitro #MHC class I #MHC class II #Major histocompatibility complex #Proteasome #Protein subunit #T cell #Ubiquitin and proteasome pathways #vaccines and immunoinformatics approaches

paper · doi:10.1126/science.1141915

published in Science 316(5829), 1349-1353 (American Association for the Advancement of Science)

openalex publication_date 2007/05/31 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/23

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 beta5t. beta5t 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 beta5t into proteasomes in place of beta5 or beta5i selectively reduces this activity. We also found that beta5t-deficient mice displayed defective development of CD8(+) T cells in the thymus. Our results suggest a key role for beta5t in generating the MHC class I-restricted CD8(+) T cell repertoire during thymic selection.

Citations

• Structure of 20S proteasome from yeast at 2.4Å resolution
• 26S proteasomes and immunoproteasomes produce mainly N‐extended versions of an antigenic peptide
• Proteasome from Thermoplasma acidophilum : a Threonine Protease
• STRUCTURE AND FUNCTIONS OF THE 20S AND 26S PROTEASOMES

Cited by

• Proteasome Activators
• Molecular mechanisms of proteasome assembly
• Proteasome [wikipedia]

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