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ID 113736
Author
Ohte, Yuki University of Tokyo
Setoh, Kazuya Kyoto University
Nakase, Hiroshi University of Tokushima
Maekawa, Akiko University of Tokushima
Kiyonari, Hiroshi RIKEN Center
Hamazaki, Yoko Kyoto University
Sekai, Miho Kyoto University
Sudo, Tetsuo Kyoto University
Tabara, Yasuharu Kyoto University
Sawai, Hiromi University of Tokyo
Omae, Yosuke University of Tokyo
Yuliwulandari, Rika YARSI University
Tanaka, Yasuhito Nagoya City University
Mizokami, Masashi National Center for Global Health and Medicine
Inoue, Hiroshi University of Tokushima
Kasahara, Masanori Hokkaido University
Minato, Nagahiro Kyoto University
Tokunaga, Katsushi University of Tokyo
Tanaka, Keiji Tokyo Metropolitan Institute of Medical Science
Matsuda, Fumihiko Kyoto University
Murata, Shigeo University of Tokyo
Content Type
Journal Article
Description
The Psmb11-encoded β5t subunit of the thymoproteasome, which is specifically expressed in cortical thymic epithelial cells (cTECs), is essential for the optimal positive selection of functionally competent CD8+ T cells in mice. Here, we report that a human genomic PSMB11 variation, which is detectable at an appreciable allele frequency in human populations, alters the β5t amino acid sequence that affects the processing of catalytically active β5t proteins. The introduction of this variation in the mouse genome revealed that the heterozygotes showed reduced β5t expression in cTECs and the homozygotes further exhibited reduction in the cellularity of CD8+ T cells. No severe health problems were noticed in many heterozygous and 5 homozygous human individuals. Long-term analysis of health status, particularly in the homozygotes, is expected to improve our understanding of the role of the thymoproteasome-dependent positive selection of CD8+ T cells in humans.
Journal Title
JCI Insight
ISSN
23793708
Publisher
American Society for Clinical Investigation
Volume
2
Issue
10
Start Page
e93664
Published Date
2017-05-18
Rights
Open Access Journal
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences