Differential regulation of MHC II and invariant chain expression during maturation of monocyte-derived dendritic cells

Abstract

DCs are potent initiators of adaptive immune responses toward invading pathogens. Upon reception of pathogenic stimuli, DCs initiate a complex differentiation program, culminating in mature DCs with an extreme capacity to activate naïve T cells. During this maturation, DCs reduce the synthesis and turnover of MHC II molecules. This allows for a stable population of MHC II, presenting peptides captured at the time and place of activation, thus provoking specific immune responses toward the activating pathogen. The efficient loading of antigenic peptides onto MHC II is vitally dependent on the accessory molecule Ii, which aids in the assembly of the MHC II α- and β-chains in the ER and directs their trafficking to the endocytic compartments, where they encounter endocytosed antigen. However, Ii plays additional roles in DC function by influencing migration, antigen uptake, and processing. To examine the biosynthetic background for diverse Ii functions in DCs, we investigated mRNA and protein levels of Ii compared with MHC II in human moDCs during maturation using various stimuli. We find that the production of Ii did not correlate with that of MHC II and that mature DCs maintain abundant levels of Ii despite a reduced production of new MHC II.