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

Abstract

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.

Keywords: antigen presentation; cross-presentation; dendritic cell subsets; immunotherapy.

Figure 1

Decisive factors in dendritic cell (DC) cross-presentation. The ability of DCs to cross-present antigens is not just an intrinsic property of the specific DC subset, but is also determined by: (i) type of antigen; (ii) presence of DC stimulatory factors; and (iii) timing and phase of the immune response. DCs encounter antigens of many origins, shapes, and sizes. The ability of DCs to internalize soluble antigens, immune complexes, dying cells, or whole pathogens is largely determined by the repertoire of antigen uptake receptors (e.g., Fc receptors, CD36, and C-type lectins) and the ability to engulf antigens through receptor-independent processes. The dynamic endocytic receptor expression is, in turn, affected by ligation of pattern-recognition receptors [PRRs; e.g., Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-like helicases (RLHs)] recognizing a particular group of pathogens expressing a unique set of pathogen- or danger-associated molecular patterns (PAMPs/DAMPs). These stimuli are also able to modulate the intracellular mechanisms of cross-presentation, emphasizing the significance of different adjuvants used in different studies. In addition, the surrounding cellular and soluble factors in the micro-milieu can significantly alter the cross-presenting potential of DCs. The effects of all these modulating factors are concordantly dependent on the timing relative to antigen processing by the DCs and thereby affect the outcome for T cell activation in different phases of the immune response.