@article{10.1172/jci.insight.93664, author = {Izumi Ohigashi AND Yuki Ohte AND Kazuya Setoh AND Hiroshi Nakase AND Akiko Maekawa AND Hiroshi Kiyonari AND Yoko Hamazaki AND Miho Sekai AND Tetsuo Sudo AND Yasuharu Tabara AND Hiromi Sawai AND Yosuke Omae AND Rika Yuliwulandari AND Yasuhito Tanaka AND Masashi Mizokami AND Hiroshi Inoue AND Masanori Kasahara AND Nagahiro Minato AND Katsushi Tokunaga AND Keiji Tanaka AND Fumihiko Matsuda AND Shigeo Murata AND Yousuke Takahama}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {A human PSMB11 variant affects thymoproteasome processing and CD8+ T cell production}, year = {2017}, month = {5}, volume = {2}, url = {https://insight.jci.org/articles/view/93664}, abstract = {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.}, number = {10}, doi = {10.1172/jci.insight.93664}, url = {https://doi.org/10.1172/jci.insight.93664}, }