Differential Expression Regulation of the α and β Subunits of the PA28 Proteasome Activator in Mature Dendritic Cells

Abstract

Activation of dendritic cells (DC) by Th-dependent (CD40) or -independent (LPS, CpG, or immune complexes) agonistic stimuli strongly enhances the expression of the proteasome activator PA28αβ complex. Upon activation of DC, increased MHC class I presentation occurred of the melanocyte-associated epitope tyrosinase-related protein 2180-188 in a PA28αβ-dependent manner. In contrast to other cell types, regulation of PA28αβ expression in DC after maturation was found to be IFN-γ independent. In the present study, we show that expression of PA28α and β subunits was differentially regulated. Firstly, PA28α expression is high in both immature and mature DC. In contrast, PA28β expression is low in immature DC and strongly increased in mature DC. Secondly, we show the presence of a functional NF-κB site in the PA28β promoter, which is absent in the PA28α promoter, indicating regulation of PA28β expression by transcription factors of the NF-κB family. In addition, glycerol gradient analysis of DC lysates revealed elevated PA28αβ complex formation upon maturation. Thus, induction of PA28β expression allows proper PA28αβ complex formation, thereby enhancing proteasome activity in activated DC. Therefore, maturation of DC not only improves costimulation but also MHC class I processing. This mechanism enhances the CD8+ CTL (cross)-priming capacity of mature DC.