Control of MHC class II antigen presentation in dendritic cells: a balance between creative and destructive forces

The antigen capturing and presenting abilities of dendritic cells (DCs) are developmentally regulated in a process known as maturation. During maturation, DCs increase several fold their surface expression of major histocompatibility complex class II (MHC II) molecules. This increase is accompanied with a dramatic change in localization of MHC II molecules, which are abundant in endosomal structures in immature DCs but located mostly on the plasma membrane in mature DCs. How these changes relate to antigen processing, generation of MHC II-peptide complexes, and trafficking of MHC II molecules, in the immature and mature states of DC development, has been a matter of debate. Here, we discuss the work carried out to characterize the biochemical and cell biological mechanisms that control MHC II antigen presentation in mouse and human DCs, and how these mechanisms relate to the function of the DC network in vivo. We conclude that the control checkpoints operate downstream of MHC II-peptide complex formation and expression on the plasma membrane, acting in accord with control of MHC II synthesis. Therefore, immature and mature DCs present antigens to T cells under steady state and inflammatory conditions. We advocate that the mechanisms regulating MHC II-peptide complex turnover should be emphasized as an important theme for future DC research.