The effect of forcibly expressed “immunoproteasome” subunit β5i in cortical thymic epithelial cells (36.46)

Abstract

Abstract Cortical thymic epithelial cells (cTECs) provide an essential microenvironment for the positive selection of MHC-restricted T cells. Data in recent years suggests that a novel proteasome subunit—β5t, exclusively expressed in cTECs in the thymus, plays a key role in generating the MHC Class I-restricted CD8+ T cell repertoire during thymic selection. In contrast, the “immunoproteasome” subunit β5i is normally expressed in dendritic cells and medullary thymic epithelial cells, and can be upregulated in other MHC Class I positive cells by IFNγ. To study how positive selection is regulated by a unique peptide repertoire expressed in cTEC, we generated K14-β5i transgenic (Tg) mice in which β5i was expressed in cTECs under the control of the human keratin 14 (K14) promoter. Forced expression of β5i in cTECs did not result in a reduced percentage or number of CD8 T cells. However, there was an increase in the percentage and number of CD44high “memory phenotype” CD8 T cells in the periphery of K14- β5i Tg mice, similar to that observed in β5t deficient mice. This suggests that the expression of β5i in cTECs could induce a distinct peptide repertoire and affect the selection of CD8 T cells in thymus. In addition, these mice exhibit hyperkeratosis of the skin. RAG-deficiency did not rescue the skin disease of K14-β5i Tg mice, indicating that it might be promoted by the over-expression of β5i in keratinocytes.