Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo

Key Points Dendritic cells (DCs) are heterogeneous. The migratory DCs traffic from tissues to lymph nodes, where they mature. The resident DCs spend their entire lifespan in the lymphoid organs in an immature state until activated by signals reaching these organs. Both migratory and resident DCs can be subdivided into several subtypes with different roles in antigen presentation. Endogenous antigenic peptides (that is, those derived from proteins synthesized by the DCs themselves) are presented on MHC class I and II molecules by all DCs and across all maturational states. Variability in antigen capture (through differential expression of endocytic mechanisms or receptors) can dictate the part played by each DC subset in the presentation of exogenous antigens. Additional differences in the expression of components of the cross-presentation machinery, and in antigen handling, further determine the role of each DC in MHC class II presentation and MHC class I cross-presentation. Resident DCs have important roles in the presentation of antigens from blood pathogens; CD8 + DCs are biased towards MHC class I cross-presentation and CD8 − DCs are biased towards MHC class II presentation. Self and pathogen antigens located in peripheral tissues are brought to lymph nodes by migratory DCs, which present the antigens on MHC class II molecules. These antigens can be transferred to resident CD8 + DCs, which then present the antigens on MHC class II molecules, and also cross-present them through the MHC class I pathway. Cooperation between migratory and resident DC subsets allows the exploitation of the intrinsic properties of each DC subset in order to optimize the capacity of the DC network to respond efficiently to different scenarios of infection.