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

Nature Reviews Immunology volume 7, pages 543–555 (2007)Cite this article

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.

Abstract

Dendritic cells (DCs) comprise several subsets, and their roles in the presentation of antigens derived from pathogens, vaccines and self tissues are now beginning to be elucidated. Differences in location, life cycle and intrinsic abilities to capture, process and present antigens on their MHC class I and class II molecules enable each DC subset to have distinct roles in immunity to infection and in the maintenance of self tolerance. Unexpected interactions among DC subsets have also been revealed. These interactions, which allow the integration of the intrinsic abilities of different DC types, enhance the ability of the DC network to respond to multiple scenarios of infection.

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Figure 1: The developmental pathway of migratory and lymphoid-organ-resident DCs.
Figure 2: The antigen-presentation pathways in dendritic cells.
Figure 3: The antigen-presenting functions of migratory and resident dendritic-cell populations in three hypothetical scenarios of tissue infection.

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Acknowledgements

We thank F. Carbone, B. Heath, C. Kurts and K. Shortman for helpful discussions. Our work is supported by grants from the National Health and Medical Research Council of Australia and the Anti-Cancer Council of Australia (J.A.V.), a Leukemia and Lymphoma Society Scholarship (J.A.V.), and a Gottlieb Daimler- and Karl Benz-Foundation Fellowship (P.S.).

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  1. The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, 3050, Victoria, Australia

    José A. Villadangos

  2. Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, D-69120, Germany

    Petra Schnorrer

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Glossary

Toll-like receptor

(TLR). A member of a family of receptors that is homologous to Drosophila melanogaster Toll. TLRs recognize conserved molecular patterns that are unique to microorganisms. The lipopolysaccharide component of bacterial cell walls is one such component. TLRs can also recognize mammalian components and contribute to autoimmunity.

Nucleotide-binding oligomerization domain (NOD) proteins

Members of a family that includes the apoptosis regulator APAF1 (apoptotic-protease-activating factor 1), mammalian NOD-LRR proteins (also known as NACHT-LRR proteins or CATERPILLERs) and plant disease-resistance gene products. Several NOD proteins have been implicated in the induction of nuclear factor-κB activity and in the activation of caspases.

RIG-I-like receptors

A family of cytoplasmic pathogen sensors that recognize viral double-stranded RNA molecules and trigger an antiviral response.

C-type lectin receptors

A large family of receptors that bind glycosylated ligands and have multiple roles, such as in cell adhesion, endocytosis, natural-killer-cell target recognition and dendritic-cell activation.

Proteasome

A giant multicatalytic protease that is resident in the cytosol and the nucleus.

Cathepsins

A class of proteases that are localized mainly in lysosomes and lysosome-like organelles.

Pinocytosis

Also known as fluid-phase endocytosis. A process of engulfment of extracellular fluid and its solutes. It can be mediated by an actin-dependent mechanism that can engulf large volumes (macropinocytosis) or by other mechanisms that result in engulfment of smaller volumes (micropinocytosis).

Phagocytosis

A process that is used by cells to internalize large particles, such as debris, apoptotic cells and pathogens, into phagosomes.

Negative selection

The deletion of self-reactive thymocytes in the thymus. Thymocytes expressing T-cell receptors that strongly recognize self peptide bound to self MHC molecules undergo apoptosis in response to the signalling generated by high-affinity binding.

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Villadangos, J., Schnorrer, P. Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo. Nat Rev Immunol 7, 543–555 (2007). https://doi.org/10.1038/nri2103

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