Human FcγRIIIa (V158) (GST-Fusion)

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.

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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.

Using IgG binding assay, it was found that NK cells from donors carrying FcγRIIIa-F158 genotype bind significantly less IgG1, IgG3 and IgG4 as compared with NK cells from donors carrying FcγRIIIa-V158 genotype. Interestingly, in treating non-Hodgkin lymphoma, Rituximab is much more efficacious in patients carrying FcγRIIIa-V158 genotype than those carrying the alternative polymorphic genotype, FcγRIIIa-F158.

Amino Acid Sequence

References

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4. 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.

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