Trends in Immunology
Volume 34, Issue 8, August 2013, Pages 361-370
Journal home page for Trends in Immunology

Opinion
Antigen cross-presentation by dendritic cell subsets: one general or all sergeants?

https://doi.org/10.1016/j.it.2013.02.007Get rights and content

Antigen cross-presentation describes the process through which dendritic cells (DCs) acquire exogenous antigens for presentation on MHC class I molecules. The ability to cross-present has been thought of as a feature of specialized DC subsets. Emerging data, however, suggest that the cross-presenting ability of each DC subset is tuned by and dependent on several factors, such as DC location and activation status, and the type of antigen and inflammatory signals. Thus, we argue that capacity of cross-presentation is not an exclusive trait of one or several distinct DC subtypes, but rather a common feature of the DC family in both mice and humans. Understanding DC subset activation and antigen-presentation pathways might yield improved tools and targets to exploit the unique cross-presenting capacity of DCs in immunotherapy.

Section snippets

DCs and antigen cross-presentation

DCs are professional antigen-presenting cells (APCs) that are uniquely capable of attracting and activating naïve CD4+ and CD8+ T cells. After infection or inflammation, DCs undergo a complex maturation process, and migrate to lymph nodes (LNs) where they present antigens to T cells. Immature DCs acquire exogenous antigens, which they can present on MHC class I molecules via the process of cross-presentation. Cross-presentation is thought to occur through one of two main pathways [1]. The

Phenotype and cross-presentation capacity of DC subsets in mice

Genetic profiling has identified a common origin of many DC subsets together with the transcription factors needed for DC lineage commitment (Box 1) 25, 26, 27, 28, 29. An outstanding question is whether efficient cross-presentation is an exclusive trait of some DC subpopulations or a common feature of many or even all DCs.

Cross-presenting capacity of human blood DC subsets

cDCs and pDCs are the two main subtypes distinguished in the blood. The cDC subset can be further divided into at least two subtypes by the expression of CD11c in combination with CD1c blood dendritic cell antigen (BDCA)1 and CD141 (BDCA3) 86, 87. BDCA1+ DCs are presented as the human counterpart of murine CD11b+ DCs 25, 26. In contrast to murine CD11b+ DCs, blood-derived BDCA1+ DCs cross-present cell-associated 2, 8, 88, 89, 90, long peptides [91], soluble antigens 81, 89, 90, 92, 93, as well

Factors influencing cross-presenting capacity

The capacity to cross-present exogenous antigens may not be restricted to a specialized DC subset. Rather, it seems that a cross-presentation program can be initiated in most if not all DC subsets. Factors emerging as important for the modulation of the cross-presentation activity of specific DC subsets are: (i) type of antigen; (ii) presence of DC stimulatory factors, which can be altered by pathogens or adjuvants; and (iii) timing and phase of the immune response.

Concluding remarks

Available data suggest that all the classically characterized DC subsets have the ability to cross-present exogenous antigens. The type of antigen and presence and timing of inflammatory signals and other components of the microenvironment that program DC differentiation and activation are decisive in determining which DC subsets become dominant and sometimes indispensable for cross-presentation. Understanding the functional reprogramming of distinct DC subsets under different inflammatory

Acknowledgments

Limitations of space preclude extensive citation of the literature; we apologize to those whose work is not mentioned in this review. This work was supported by grants from the Dutch Cancer Society (KWF2008-4617), The Netherlands Organization for Scientific Research (NWO-Vici-918.66.615), and the Netherlands Institute for Regenerative Medicine (NIRM, grant No. FES0908).

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