Role of IgG and IgE FcR in antigen presentation

The first critical step in the chain of events leading to activation of T and B lymphocytes by an exogenous antigen, whether a vaccine molecule or a pathogenic organism, is efficient uptake of the antigen by professional antigen presenting cells (APCs). Antigens are concentrated by APCs both by high-rate fluid phase pinocytosis referred to as macropinocytosis, and by receptor-mediated uptake via, for example, mannose receptors on dendritic cells or surface immunoglobulin on B cells [reviewed in Reference 1]. The mechanism of uptake determines the intracellular compartment in which the antigen is processed, and this in turn influences the repertoire of peptides produced and the types of T cells stimulated. Pioneering studies by Cohen et al. in 1972 suggested that Fc receptors can play a critical role in the uptake of antigen by APCs. These authors demonstrated that the dose of antigen required for T cell activation could be reduced over 100-fold in the presence of antigen-specific IgG antibodies [2]. As detailed elsewhere in this volume, Fc receptors comprise an extensive and well characterized family of molecules that specifically bind IgG, IgA or IgE. Since individual Fc receptors are selectively expressed on some APCs but not on others, and exhibit differential binding of immunoglobulins (reviewed in Chapter 2), the presence, amount, class and subclass of antigen-specific antibodies can play a critical role in determining which APCs participate most efficiently in lymphocyte activation. This chapter provides an overview of the capacity of particular IgG and IgE Fc receptors to mediate antibody-enhanced antigen presentation, and lays the foundation for the possible use of Fc receptor-targeted antigens to enhance the potency of vaccines.