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

Nat Immunol. 2014 Aug;15(8):707-16. doi: 10.1038/ni.2939.


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.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity*
  • Amino Acid Sequence
  • Antibodies / immunology
  • Antigen Presentation / immunology
  • Autoimmune Diseases / immunology
  • Glycosylation
  • Humans
  • Immunity, Innate*
  • Immunoglobulin Fc Fragments / chemistry
  • Immunoglobulin Fc Fragments / classification
  • Immunoglobulin Fc Fragments / immunology*
  • Immunoglobulin G / immunology
  • Neoplasms / immunology
  • Protein Conformation
  • Protein Structure, Tertiary
  • Receptors, IgG / chemistry
  • Receptors, IgG / classification
  • Receptors, IgG / immunology*
  • Vaccination


  • Antibodies
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Receptors, IgG