Abstract
The cellular uptake, intracellular processing, and presentation of foreign antigen are crucial processes for eliciting an effective adaptive host response to the majority of pathogens. The effective recognition of antigen by T cells requires that it is first processed and then presented on MHC molecules that are expressed on other cells. A critical step leading to the presentation of antigen is delivering the foreign cargo to an intracellular compartment where the antigen can be processed and loaded onto MHC molecules. Fc-gamma receptors (FcγRs) recognize IgG-coated targets, such as opsonized pathogens or immune complexes (ICs). Cross-linking leads to internalization of the cargo with associated activation of down-stream signaling cascades. FcγRs vary in their affinity for IgG and intracellular trafficking, and therefore have an opportunity to regulate antigen presentation by controlling the shuttling and processing of their cargos. In this way, they critically influence physiological and pathophysiological adaptive immune cell functions. In this review, we will cover the contribution of FcγRs to antigen-presentation with a focus on the intracellular trafficking of IgG-ICs and the pathways that support this function. We will also discuss genetic evidence linking FcγR biology to immune cell activation and autoimmune processes as exemplified by systemic lupus erythematosus (SLE).
Highlights
The immune response can be divided broadly into innate and adaptive immunity
The Fc gamma receptor (FcγR) family provides a critical point of control for regulating antigen presentation of Immunoglobulin type G (IgG)-coated antigens
This control can be exerted at several stages such as the internalization of antigen, directing intracellular antigen transport, and by controlling subsequent signaling events that lead to the presentation of antigen
Summary
The immune response can be divided broadly into innate and adaptive immunity. Innate immune cells, such as dendritic cells, monocytes, NK cells, and neutrophils among others, mount early responses to pathogens through recognition of conserved non-host pattern antigens, such as bacterial lipopolysaccharide (LPS) or viral RNA [1, 2]. Antigens contained in the endosomal compartment can be shuttled into the cytoplasm, where they are processed to conventional cytosolic antigens relying on TAP and proteasome function [23] Lysosomal proteases such as cathepsin S have been suggested to degrade exogenous antigens already in the acidic compartment [24], where peptides are loaded to intra-endosomal MHC class I molecules. This latter cross-presentation process has been termed the “vacuolar pathway” and exists for example in certain viral or bacterial infections [25]. Entry of these antigens into the endolysosomal system for delivery to MHC II compartments can be facilitated by both Lamp-2a [27] and autophagy [28]
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