Human FcγRIIa (R131) (GST-Fusion)

Human FcRIIa has 2 allotypes, the H131 and R131. FcRIIa H131 exhibits a higher affinity to human IgG1 and IgG2 than the FcRIIa R131 does and is thought to be primarily responsible for the phagocytosis of the IgG-opsonized bacteria. 

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Quick Spec

Description

The first quarter of antibodies contain variable regions capable of recognizing a great variety of antigens. The second half of antibodies contains the Fc domain with limited variation and is critical for bringing together the bound-antigen with cellular effector functions. The IgG Fc receptors which mediate the effector functions are expressing on leukocytes and are composed of three major classes: FcγR1 (CD64), FcγRII (CD32) and FcγRIII (CD16).

In human, the latter two contain subgroups: FcγRIIa and FcγRIIb, as well as FcγRIIIa and FcγRIIIb. Structurally, each FcγR contains the α chain which is a member of Ig superfamily and is directly interacting with the Ig Fc. Of importance, the α chain of FcγRII receptors contains the signalling motif of either ITAM (immunoreceptor tyrosine-based activation motif) or ITIM (immunoreceptor tyrosine-based inhibition motif). In contract, the ITAM or ITIM motif is absence from FcγRI and FcγRIII receptors, instead the signalling transduction of these receptor is mediated through the accessory proteins, γγ homodimer or γζ heterodimer which contains the ITAM motif.

FcγRIIb is the only FcγR contains the ITIM, hence the sole inhibitory receptor. For binding to human IgG1, FcγRI exhibits a high affinity in the nM (10-8-10-9) range and can bind monomeric IgG. In contrast, the FcγRII and FcγRIII interacts with monomeric IgG with a much weaker affinity at the tenths of uM (10-7) range.

Amino Acid Sequence

References

1. Xu Y, Wei HT, Zou JJ, Ma YR. Association of FcγRIIA-R/H131 polymorphism and systemic lupus erythematosus lupus nephritis risk: A meta-analysis. Int J Rheum Dis. 2020;23(7):853-67. Epub 20200318. doi: 10.1111/1756-185x.13815. PubMed PMID: 32189478.

2. Bournazos S, Gupta A, Ravetch JV. The role of IgG Fc receptors in antibody-dependent enhancement. Nat Rev Immunol. 2020;20(10):633-43. Epub 20200811. doi: 10.1038/s41577-020-00410-0. PubMed PMID: 32782358; PubMed Central PMCID: PMC7418887.

3. Gessner JE, Heiken H, Tamm A, Schmidt RE. (1998) The IgG Fc receptor family. Ann Hematol. 76231-248.

4. Maenaka K, van der Merwe PA, Stuart DI, Jones EY, Sondermann P. (2001) The human low affinity Fcgamma receptors IIa, IIb, and III bind IgG with fast kinetics and distinct thermodynamic properties. J Biol Chem. 276:44898-44904.

5. Mechetina LV, Najakshin AM, Alabyev BY, Chikaev NA, Taranin AV. (2002) Identification of CD16-2, a novel mouse receptor homologous to CD16/Fc gamma RIII. Immunogenetics. 54:463-468.

6. Nimmerjahn F, Bruhns P, Horiuchi K, Ravetch JV. (2005) FcgammaRIV: a novel FcR with distinct IgG subclass specificity. Immunity 23:41-51.