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

JCI Insight
Izumi OhigashiYousuke Takahama

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.

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Citations

Nov 27, 2018·International Immunology·Kenta KondoYousuke Takahama
Aug 15, 2018·Nature Immunology·Shigeo MurataKeiji Tanaka
May 28, 2020·Frontiers in Immunology·Abdullah S AlawamBeth Lucas
Mar 4, 2021·Pathology International·Masanori Kasahara
Apr 6, 2021·Frontiers in Immunology·Melina FrantzeskakisIzumi Ohigashi

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Methods Mentioned

BETA
PCR
genotyping
flow cytometry

Software Mentioned

FlowJo

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