Fc receptor
Immunoglobulin-like receptor | |
---|---|
Identifiers | |
Symbol | Fc receptor |
Membranome | 10 |
In
Classes
There are several different types of Fc receptors (abbreviated FcR), which are classified based on the
Fc-gamma receptors
All of the Fcγ receptors (FcγR) belong to the
The Fc-gamma receptors differ in their affinity for IgG and likewise the different IgG subclasses have unique affinities for each of the Fc gamma receptors.[6] These interactions are further tuned by the glycan (oligosaccharide) at position CH2-84.4 of IgG.[6] For example, by creating steric hindrance, fucose containing CH2-84.4 glycans reduce IgG affinity for FcγRIIIA.[6] In contrast, G0 glycans, which lack galactose and terminate instead with GlcNAc moieties, have increased affinity for FcγRIIIA.[6]
Neonatal Fc Receptor
Another FcR is expressed on multiple cell types and is similar in structure to
Recently, research suggested that this receptor plays a role in the homeostasis of IgG serum levels.Fc-alpha receptors
Only one Fc receptor belongs to the FcαR subgroup, which is called FcαRI (or CD89).
Fc-epsilon receptors
Two types of FcεR are known:[3]
- the high-affinity receptor FcεRI is a member of the immunoglobulin superfamily (it has two Ig-like domains). FcεRI is found on epidermal Langerhans cells, eosinophils, mast cells and basophils.[13][14] As a result of its cellular distribution, this receptor plays a major role in controlling allergic responses. FcεRI is also expressed on antigen-presenting cells, and controls the production of important immune mediators called cytokines that promote inflammation.[15]
- the low-affinity receptor FcεRII (CD23) is a C-type lectin. FcεRII has multiple functions as a membrane-bound or soluble receptor; it controls B cell growth and differentiation and blocks IgE-binding of eosinophils, monocytes, and basophils.[16]
Summary table
Receptor name | Principal antibody ligand | Affinity for ligand | Cell distribution | Effect following binding to antibody |
FcγRI (CD64) | IgG1 and IgG3 | High (Kd ~ 10−9 M) | Dendritic cells
|
Phagocytosis Cell activation Activation of respiratory burst Induction of microbe killing |
FcγRIIA (CD32) | IgG | Low (Kd > 10−7 M) | Macrophages Neutrophils Eosinophils Langerhans cells
|
Phagocytosis Degranulation (eosinophils) |
FcγRIIB1 (CD32) | IgG | Low (Kd > 10−7 M) | Mast cells
|
No phagocytosis Inhibition of cell activity |
FcγRIIB2 (CD32) | IgG | Low (Kd > 10−7 M) | Macrophages Neutrophils Eosinophils |
Phagocytosis Inhibition of cell activity |
FcγRIIIA ( CD16a )
|
IgG | Low (Kd > 10−6 M) | Macrophages (certain tissues)
|
Induction of antibody-dependent cell-mediated cytotoxicity (ADCC)Induction of cytokine release by macrophages |
FcγRIIIB ( CD16b )
|
IgG | Low (Kd > 10−6 M) | Eosinophils Macrophages Neutrophils Mast cells Follicular dendritic cells |
Induction of microbe killing |
FcεRI
|
IgE | High (Kd ~ 10−10 M) | Mast cells Eosinophils Basophils Langerhans cells Monocytes |
Degranulation Phagocytosis |
FcεRII (CD23) | IgE | Low (Kd > 10−7 M) | B cells Eosinophils Langerhans cells |
Possible adhesion molecule IgE transport across human intestinal epithelium Positive-feedback mechanism to enhance allergic sensitization (B cells) |
FcαRI ( CD89 )
|
IgA | Low (Kd > 10−6 M) | Monocytes Macrophages Neutrophils Eosinophils |
Phagocytosis Induction of microbe killing |
Fcα/μR (CD351) | IgA and IgM | High for IgM, Mid for IgA | B cells Mesangial cells Macrophages |
Endocytosis Induction of microbe killing |
FcμR[17] | IgM | (unknown) | Human FcμR is predominantly expressed by lymphocytes, but not by phagocytes [18] | function has not been fully elucidated / diverse [19] |
FcRn
|
IgG | high in acidic cellular endosomes low in pH neutral extracellular environment |
Monocytes Macrophages Endothelial cells Hepatocytes |
Transfers IgG from a mother to fetus through the placenta Transfers IgG from a mother to infant in milk Protects IgG from degradation Transfers IgG across endothelial/epithelial layers |
Functions
Fc receptors are found on a number of cells in the immune system including phagocytes like macrophages and monocytes, granulocytes like neutrophils and eosinophils, and lymphocytes of the innate immune system (natural killer cells) or adaptive immune system (e.g., B cells).[20][21][22] They allow these cells to bind to antibodies that are attached to the surface of microbes or microbe infected cells, helping these cells to identify and eliminate
Signaling mechanisms - Fc gamma receptors
Activation
Fc gamma receptors belong to the group of
Inhibition
The presence of only one YXXL motif is not sufficient to activate cells, and represents a motif (I/VXXYXXL) known as an
The negative signaling by FcγRIIB is mainly important for regulation of activated B cells. The positive B cell signaling is initiated by binding of foreign antigen to surface immunoglobulin. The same antigen-specific antibody is secreted and it can feedback-suppress, or promote negative signaling. This negative signaling is being provided by FcγRIIB.:
Cellular activation
On phagocytes
When
On NK cells
The Fc receptor on NK cells recognize IgG that is bound to the surface of a pathogen-infected target cell and is called CD16 or FcγRIII.
On mast cells
On eosinophils
Large parasites like the
On T lymphocytes
CD4+ T cells (mature Th cells) provide help to B cells that produce antibodies. Several subsets of activated effector CD4+ T cells are observed in disease pathology. Earlier studies summarized by Sanders and Lynch in 1993 suggested critical roles for FcRs in CD4+ T cell mediated immune responses and proposed the formation of a joint signaling complex among FcRs and TCR on the cell surface.[41][42][43][44] Chauhan and coworkers reported the colocalization of the labeled ICs with the CD3 complex on activated CD4+ T cell surface, which thus suggest the coexistence of FcRs together with TCR complex.[45] Both of these receptors are observed forming an apical structure on the membrane of activated CD4+ T cells, suggesting the lateral movement of these receptors.[46] Co-migration of FcRs with TCR and BCR complex is observed on the cells surface and T:B cell cytoconjugates show this coexistence at the point of contact.[47] An earlier review suggested that the expression of FcRs on CD4+ T cells is an open question.[48] This established the current paradigm that T cells do not express FcRs and these findings were never challenged and experimentally tested.[49] Chauhan and coworkers showed binding of immune complexes (ICs), the FcR ligand to activated CD4+ T cells.[49] CD16a expression is induced in the activated human naïve CD4+ T cells, which express CD25, CD69, and CD98 and ligation to ICs leads to generation of effector memory cells.[50] CD16a signaling is mediated by phosphorylation of Syk (pSyk).[50][51][52]
A study now suggests induced expression of CD32a upon activation of human CD4+ T cells, similar to CD16a.[51][53] CD32a expression on CD4+ T cells was also suggested by three independent studies from HIV-1 researchers. The expression of CD16a and CD32a in a subset of activated CD4+ T cells is now confirmed.[51][53] FcRs on the cell surface upon binding to ICs composed of nucleic acids trigger cytokine production and upregulate nucleic acid sensing pathways. FcRs are present both on the cell surface and in the cytosol. CD16a signaling upregulate the expression of nucleic acid sensing toll-like receptors and relocate them to cell surface.[50][54] CD16a is a new costimulatory signal for human CD4+ T cells, which successfully substitute the CD28 requirement during autoimmunity.[55] In an autoimmune background CD4+ T cells bypass the requirement of CD28 cosignaling to become fully activated.[55] Furthermore, the blockade of CD28 cosignaling does not inhibit the development of TFH cells, a key subset for the generation of autoantibody producing autoreactive plasma B cells.[56] A balance among costimulatory and inhibitory signals is required for immune homeostasis. Excessive costimulation and/or insufficient co-inhibition leads to the tolerance-breakdown and autoimmunity. CD16a mediated costimulation provides a positive signal in the activated CD4+ T cells and not in the quiescent cells which lack FcγR expression.[51]
See also
References
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Further reading
- Janeway CA, Travers P, Waldport M, Shlomchik MJ (2001). "Chapter 9. The Humoral Immune Response". Immunobiology: The Immune System in Health and Disease (5th ed.). New York: Garland. ISBN 978-0-8153-3642-6.
- Abbas AK, Lichtman AH, Pillai S (2012). "Chapter 12: Effector Mechanisms of Humoral Immunity". Cellular and molecular immunology (7th ed.). Philadelphia: Elsevier/Saunders. ISBN 978-1-4377-1528-6.
- Gerber JS, Mosser DM (February 2001). "Stimulatory and inhibitory signals originating from the macrophage Fcgamma receptors". Microbes and Infection. 3 (2): 131–9. PMID 11251299.
- Maverakis E, Kim K, Shimoda M, Gershwin ME, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB (February 2015). "Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: a critical review". Journal of Autoimmunity. 57: 1–13. PMID 25578468.
External links
- Fc+Receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)