Fc Receptors

Shamir Jacobino, University Medical Center, Utrecht, The Netherlands
Anne Slomp, University Medical Center, Utrecht, The Netherlands
Peter Boross, University Medical Center, Utrecht, The Netherlands
Jeanette HW Leusen, University Medical Center, Utrecht, The Netherlands

Published online: March 2013

DOI: 10.1002/9780470015902.a0000916.pub3

Receptors for the Fc region of immunoglobulins (Igs) play a central role during an immune response as they link humoral responses to cellular activities. The majority of these leucocyte Fc receptors exist as heterooligomeric complexes with unique ligand-binding chains and promiscuous accessory subunits involved in intracellular signal transduction. In humans, five major Fc receptor classes are known, FcR for IgG, FcR for IgA, FcR for IgE, FcR for IgM and FcR for IgD. Integration of both activating and inhibitory signals occurs on Ig-Fc engagement of Fc receptors. Given their vital role in maintaining balanced immunity, dysregulation of Fc receptor function may lead to inflammatory or autoimmune disease. As such, much effort is focussed on identifying which single nucleotide polymorphisms and copy number variations in Fc receptor genes are linked with disease and understanding of how these affect therapeutic options.

Key Concepts:

  • Fc receptors link the humoral and cellular arms of the immune system.
  • Cellular activities may be triggered by Fc receptor chains independent of FcR chains.
  • Fc receptor ITAM and ITIM motifs transmit opposite signals to control leucocyte activation.
  • Inside-out regulation of Fc receptors influences their affinity for immunoglobulin ligands.
  • Fc receptor genetic variations are linked with inflammation, autoimmunity and cancer.

Keywords: Fc receptors; CD64; CD32; CD16; CD89

Figure 1. Schematic representation of human Fc receptors. The extracellular parts of most human Fc receptors are composed of varying amounts (1–5) of immunoglobulin domains. The two exceptions are the lectin family member FcRII and the major histocompatibility complex (MHC) class I protein family member FcRn. Based on their function FcRs can mediate activating signals via ITAM (green box) which consist of YxxLxxxxxxxYxxL (Y=tyrosine, L=leucine, X=any amino acid). The ITAM can either be located on the intracellular part of the receptors (FcRIIa and FcRIIc) or on the associated chain (FcRI, FcRIIIa, FcRI and FcRI). Next to its role in signalling, the chain (in blue) is also essential for surface expression. The sole inhibiting FcR, FcRIIb, bears an ITIM (red box) on its intracellular tail, which consists of Y/V/L/S/xYxxL/V (Y, tyrosine; V, valine; S, serine; L, leucine and X=any amino acid). FcRIIIb is a glycosylphosphatidylinositol (GPI)-linked activating receptor that has no intracellular tail.
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Related Sub-Topics:

Autoimmunity | Immunoregulation | Inflammation | Diagnostics, Therapeutics and Methods | Antibodies | Structure of Cell–Cell Interactions | Protein Structure
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Article Title: Fc Receptors
 
How to Cite close
Jacobino, Shamir, Slomp, Anne, Boross, Peter, and Leusen, Jeanette HW(Mar 2013) Fc Receptors. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000916.pub3]