Fcγ receptors

Introduction

The mammalian immune system has evolved to defend organisms against pathogens by layering the specificity of the adaptive immunity on top of the ancestral innate immunity. It is Fc receptors that act as the bridge between the adaptive and innate immunity, bringing the fire power of the innate immunity’s cellular response to the site of antibody binding. In humans there are a range of Fc receptors including those for IgM, (Fc mu receptors), IgA (Fc alpha receptors), IgE (Fc epsilon receptors) and IgG (Fc gamma receptors). Although these all serve an important biological purpose it is Fc gamma receptors (FcgR or FcγR) that are of most interest in therapeutic antibody development as the majority of antibodies or related molecules in development are of the IgG subclass. For this reason, Gamma Proteins focuses on the supply of high-quality Fc gamma receptors. In humans there are five Fc gamma receptors: Fc gamma RI (FcgRI or CD64); Fc gamma RIIa (FcgRIIa or CD32a); Fc gamma RIIb (FcgRIIb or CD32b); Fc gamma RIIIa (FcgRIIIa or CD16a); and Fc gamma RIIIb (FcgRIIIb or CD16b). Gamma Proteins supplies the extra cellular domains (ECDs) for all the human Fc gamma receptors, including the polymorphic variants or allotypes for CD32a, CD16a and CD16b. All Fc gamma receptors are available in unconjugated or biotinylated formats. For more information please see our product list. For further background information on Fc gamma receptors see here.

Schematic representation of the human Fc gamma receptors: FcgRI, FcgRII and FcgRIII. These consist of an alpha (α) chain consisting of two or three immunoglobulin domains and a single transmembrane domain, with the exception of CD16b which is GPI anchored. Receptors containing an ITAM motif (green rectangle) are activatory, whereas those with an ITIM motif (red rectangle) are inhibitory. CD16b does not signal and is simply a decoy. The ITAM/ITIM motifs are either contained on the α chain or in non-covalently associated signalling adapter proteins.

Product list

Filters

Molecule
Species
Conjugate
Cat No. Species Product Description Host Sequence Tag Conjugate Purity & Activity Data Size & Price
HUGR3B2-B Human Biotinylated human Fc gamma RIIIb / CD16b (NA2) protein HEK293 G17-S200 AVI & His Biotinylated
  • SDS-PAGE
  • SEC-HPLC
  • SPR
HUGR3B2-U Human Human Fc gamma RIIIb / CD16b (NA2) protein HEK293 G17-S200 AVI & His Unconjugated
  • SDS-PAGE
  • SEC-HPLC
  • SPR
HUGR3B1-B Human Biotinylated human Fc gamma RIIIb / CD16b (NA1) protein HEK293 G17-S200 AVI & His Biotinylated
  • SDS-PAGE
  • SEC-HPLC
  • SPR
HUGR3B1-U Human Human Fc gamma RIIIb / CD16b (NA1) protein HEK293 G17-S200 AVI & His Unconjugated
  • SDS-PAGE
  • SEC-HPLC
  • SPR
HUGR3AV-B Human Biotinylated human Fc gamma RIIIa / CD16a (176V) protein HEK293 G17-Q208 AVI & His Biotinylated
  • SDS-PAGE
  • SEC-HPLC
  • SPR
HUGR3AV-U Human Human Fc gamma RIIIa / CD16a (176V) protein HEK293 G17-Q208 AVI & His Unconjugated
  • SDS-PAGE
  • SEC-HPLC
  • SPR
HUGR3AF-B Human Biotinylated human Fc gamma RIIIa / CD16a (176F) protein HEK293 G17-Q208 AVI & His Biotinylated
  • SDS-PAGE
  • SEC-HPLC
  • SPR
HUGR3AF-U Human Human Fc gamma RIIIa / CD16a (176F) protein HEK293 G17-Q208 AVI & His Unconjugated
  • SDS-PAGE
  • SEC-HPLC
  • SPR
HUGR2B-B Human Biotinylated human Fc gamma RIIb / CD32b protein HEK293 A46-P217 AVI & His Biotinylated
  • SDS-PAGE
  • SEC-HPLC
  • SPR
HUGR2B-U Human Human Fc gamma RIIb / CD32b protein HEK293 A46-P217 AVI & His Unconjugated
  • SDS-PAGE
  • SEC-HPLC
  • SPR
HUGR2AR-B Human Biotinylated human Fc gamma RIIa / CD32a (167R) protein HEK293 A36-I218 AVI & His Biotinylated
  • SDS-PAGE
  • SEC-HPLC
  • SPR
HUGR2AR-U Human Human Fc gamma RIIa / CD32a (167R) protein HEK293 A36-I218 AVI & His Unconjugated
  • SDS-PAGE
  • SEC-HPLC
  • SPR
HUGR2AH-B Human Biotinylated human Fc gamma RIIa / CD32a (167H) protein HEK293 A36-I218 AVI & His Biotinylated
  • SDS-PAGE
  • SEC-HPLC
  • SPR
HUGR2AH-U Human Human Fc gamma RIIa / CD32a (167H) protein HEK293 A36-I218 AVI & His Unconjugated
  • SDS-PAGE
  • SEC-HPLC
  • SPR
HUGR1-B Human Biotinylated human Fc gamma RI / CD64 protein HEK293 Q16-L281 AVI & His Biotinylated
  • SDS-PAGE
  • SEC-HPLC
  • SPR
HUGR1-U Human Human Fc gamma RI / CD64 protein HEK293 Q16-L281 AVI & His Unconjugated
  • SDS-PAGE
  • SEC-HPLC
  • SPR

8 reasons to use Gamma Proteins

  • Purity - Final product purity is determined by SEC-HPLC with a quality threshold >95% monomer purity.

  • Activity - Biological activity of recombinant proteins is confirmed by Surface Plasmon Resonance.

  • Mammalian expression All recombinant proteins are produced in Human Embryonic Kidney 293 (HEK293) cells, ensuring correct folding and post-translational modification.

  • Animal free - All proteins are manufactured in an animal component free platform with no carrier proteins added to the final products.

  • Reproducibility - All proteins are produced recombinantly and quality & activity is confirmed for every batch.

  • Low endotoxin - All products are prepared in an endotoxin free process to ensure they have < 1 EU/mg.

  • Site-specific biotinylation - All products contain an AVI-tag for site-specific biotinylation ensuring greater reproducibility and preferential orientation for assays.

  • Lyophilized - All products come lyophilized for longer stability and reduced environmental impact from transport.

Background

Fc gamma receptors (FcgRs or FcγRs) are type I integral membrane proteins found on the surface of most immune cells (see table below) and are the receptors for IgG. Binding of the Fc domain of IgG to an FcγR mediates a wide range of cellular responses, including phagocytosis, antibody dependent cellular cytotoxicity (ADCC) and release of cytokines. It is important to note that human FcγRs are quite different to their murine counterparts despite the common FcγR and CD numbering. It is important to appreciate this when interpreting data from mouse models and translating to human. The background information provided here focuses on human FcγRs.

FcγRs can be grouped based on their affinity for monomeric IgG. Human FcγRs consist of one high affinity receptor, FcγRI (CD64 or FcgRI) and two families of low affinity receptors, FcγRII (CD32 or FcgRII) and FcγRIII (CD16 or FcgRIII). Signaling by FcγR is mediated by immunoreceptor tyrosine-based activating (ITAM) or inhibitory (ITIM) motifs that are either in the cytoplasmic tail of the receptor or in associated signaling adaptor proteins such as the common γ-chain. Aggregation of activating FcγRs, such as through binding of multivalent ligand, results in the phosphorylation of tyrosine residues in the ITAM motif by Src family protein tyrosine kinases (PTKs) and leads to activation of cellular responses. Aggregation of inhibitor FcγR also leads to phosphorylation of tyrosine residues by Src family PTKs but the phosphorylated ITIM then serves as a binding site for phosphotyrosine phosphatases (PTPs) which dephosphorylate other proteins resulting in inhibition of activating pathways.

Table of human Fc gamma receptor classes, structures, allotypes, specificities, expression profiles and function.
For the cartoon structure images, C-terminal extracellular domains are shown as colored ovals with activatory and inhibitory motifs (ITAM and ITIM) shown as green and red rectangles respectively.

FcɣRI

CD64

FcɣRlla

CD32a

FcɣRllb

CD32b

FcɣRllc

CD32c

FcɣRllIa

CD16a

FcɣRIlIb

CD16b

Structure

Allotypes

(*not in the ECD)

167H167R 232I*232T* 57Q57stop 176F176V NA1NA2SH*

Affinity

High Low Low Low Low Low Low

Relative
specificity

lgG1:+++lgG2:-lgG3:+++lgG4:+++
lgG1:+++lgG2:+lgG3:++lgG4:+
167H hasbindingto IgG1/2/3
lgG1:+lgG2:+/-lgG3:+lgG4:+ lgG1:+lgG2:+/-lgG3:+lgG4:+
lgG1:+++lgG2:+lgG3:++lgG4:+

176v has binding to all lgG

Expression

B-cell +
T-cell
NK cell Genotype Genotype +
DC + + + Genotype +
Macro + + + Genotype +
Mono + + Subsets Genotype Subsets
Neutro Induced + Genotype Genotype +
Eosino Induced + induced
Baso + + + +
Mast Induced + Subsets Genotype + +
Platelet +
Function

Activation

Activation

Inhibition

Activation

Activation

Decoy

FcγRI
High affinity immunoglobulin gamma Fc receptor I, also known as FcgRI or CD64, is a type I integral membrane glycoprotein. CD64 is a member of the immunoglobulin superfamily and is expressed on monocytes, macrophages, dendritic cells and activated granulocytes. CD64 binds with high affinity to the Fc domain of IgG and it plays a role in antigen capture, phagocytosis of IgG/antigen complexes, and antibody-dependent cellular cytotoxicity (ADCC). CD64 is structurally