Abstract
SUMMARYβ5t 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. This Matters Arising Response article addresses the Apavaloaei et al. (2021) Matters Arising paper, published concurrently in Cell Reports.
Highlights
B5t, encoded by Psmb11, is a cortical thymic epithelial cell-specific component of the thymoproteasome, which is essential for the optimal production of functionally competent CD8+ T cells (Murata et al, 2007; Nitta et al, 2010; Xing et al, 2013; Takada et al, 2015)
It has been suggested that b5t-containing thymoproteasomes produce a cortical thymic epithelial cell (cTEC)-specific set of major histocompatibility complex (MHC) class I-associated self-peptides, which govern the positive selection of CD8+ T cells in the thymic cortex (Sasaki et al, 2015; Murata et al, 2018; Ohigashi et al, 2021)
They extracted 89 differentially expressed genes by the analysis of a partial set of our data. Our examination of those 89 genes in all sets of our RNA sequencing data along with confirmation by quantitative RT-PCR analysis clarified that only one gene, Dync1i1, in our transcriptomic data meets their definition of b5t-dependent altered abundance in cTECs
Summary
B5t 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 b5t 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. a recent article reports that b5t regulates the expression of hundreds of cTEC genes and affects both CD4+ and CD8+ thymocytes by causing oxidative stress in thymocytes. We examine the issues that they raise and conclude that, rather than regulating hundreds of genes in cTECs, b5t has a highly specific impact in cTECs on proteasome subunit composition. This Matters Arising Response article addresses the Apavaloaei et al (2021) Matters Arising paper, published concurrently in Cell Reports
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