A human PSMB11 variant affects thymoproteasome processing and CD8+ T cell production

• Ohigashi, Izumi

• Ohte, Yuki

• Setoh, Kazuya

• Nakase, Hiroshi

• Maekawa, Akiko

• Kiyonari, Hiroshi

• Hamazaki, Yoko

• Sekai, Miho

• Sudo, Tetsuo

• Tabara, Yasuharu

• Sawai, Hiromi

• Omae, Yosuke

• Yuliwulandari, Rika

• Tanaka, Yasuhito

• Mizokami, Masashi

• Inoue, Hiroshi

• Kasahara, Masanori

• Minato, Nagahiro

• Tokunaga, Katsushi

• Tanaka, Keiji

• Matsuda, Fumihiko

• Murata, Shigeo

• Takahama, Yousuke

抄録

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.

収録刊行物

• JCI Insight

  JCI Insight 2 (10), e93664-, 2017-05-18

  American Society for Clinical Investigation

キーワード

• General Medicine

詳細情報

• CRID: 1050001338827777152
• NII論文ID: 120006733720
• ISSN: 23793708
• DOI: 10.1172/jci.insight.93664
• Web Site: http://repo.lib.tokushima-u.ac.jp/113736
• Web Site: https://insight.jci.org/articles/view/93664/files/pdf
• 本文言語コード: en
• 資料種別: journal article
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