Type I and type II Fc receptors regulate innate and adaptive immunity

Abstract

Antibodies produced in response to a foreign antigen are characterized by polyclonality, not only in the diverse epitopes to which their variable domains bind but also in the various effector molecules to which their constant regions (Fc domains) engage. Thus, the antibody's Fc domain mediates diverse effector activities by engaging two distinct classes of Fc receptors (type I and type II) on the basis of the two dominant conformational states that the Fc domain may adopt. These conformational states are regulated by the differences among antibody subclasses in their amino acid sequence and by the complex, biantennary Fc-associated N-linked glycan. Here we discuss the diverse downstream proinflammatory, anti-inflammatory and immunomodulatory consequences of the engagement of type I and type II Fc receptors in the context of infectious, autoimmune, and neoplastic disorders.

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Figure 1: Reciprocal engagement of type I and type II FcRs by the IgG Fc domain.
Figure 2: Glycan-dependent modulation of Fc structure.
Figure 3: Immunomodulatory functions of type I and type II FcRs.
Figure 4: Type I FcR–mediated effector functions.
Figure 5: Both type I FcRs and type II FcRs mediate the anti-inflammatory effects of IVIG or sialylated IgG.

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Correspondence to Jeffrey V Ravetch.

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Pincetic, A., Bournazos, S., DiLillo, D. et al. Type I and type II Fc receptors regulate innate and adaptive immunity. Nat Immunol 15, 707–716 (2014). https://doi.org/10.1038/ni.2939

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