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

ABSTRACT: The Psmb11-encoded ?5t 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 ?5t amino acid sequence that affects the processing of catalytically active ?5t proteins. The introduction of this variation in the mouse genome revealed that the heterozygotes showed reduced ?5t 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.

SUBMITTER: Ohigashi I 

PROVIDER: S-EPMC5436549 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature