Regulation of Antigen Presentation and Cross-presentation in the Dendritic Cell Network: Facts, Hypothesis, and Immunological Implications

Dendritic cells (DCs) are central to the maintenance of immunological tolerance and the initiation and control of immunity. The antigen-presenting properties of DCs enable them to present a sample of self and foreign proteins, contained within an organism at any given time, to the T-cell repertoire. DCs achieve this communication with T cells by displaying antigenic peptides bound to MHC I and MHC II molecules. Here we review the studies carried out over the past 15 years to characterize these antigen presentation mechanisms, emphasizing their significance in relation to DC function in vivo. The life cycles of different DC populations found in vivo are described. Furthermore, we provide a critical assessment of the studies that examine the mechanisms controlling DC MHC class II antigen presentation, which have often reached contradictory conclusions. Finally, we review findings pertaining to the biological mechanisms that enable DCs to present exogenous antigens on their MHC class I molecules, a process known as cross-presentation. Throughout, we highlight what we consider to be major knowledge gaps in the field and speculate on possible directions for future research.