β5t is a cortical thymic epithelial cell (cTEC)-specific component of the thymoproteasome, which is essential for the optimal production of functionally competent CD8+ T cells. Our recent analysis showed a specific impact of β5t on proteasome subunit composition in cTECs, supporting the possibility that the thymoproteasome optimizes CD8+ T cell development through the production of MHC-I-associated unique self-peptides in cTECs. However, a recent article reports that β5t regulates the expression of hundreds of cTEC genes and affects both CD4+ and CD8+ thymocytes by causing oxidative stress in thymocytes. The authors further analyze our published data and describe that they confirm their conclusions. Here, we examine the issues that they raise and conclude that, rather than regulating hundreds of genes in cTECs, β5t has a highly specific impact in cTECs on proteasome subunit composition.
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