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The efficacy of a therapeutic antibody not only depends on the Fab fragment and its binding activity to the target antigen, but also depends on the Fc fragment and its interaction with key Fc receptors. The binding affinity of the Fc fragment towards FcRn (FCGRT&B2M) would predict the antibody’s half life, while that between the Fc fragment and FCGRIIIA (CD16a) would influence the antibody’s ability to elicit ADCC (antibody dependent cell mediated cytotoxicity). Hence, screening for desired binding affinity to these Fc receptors is an essential component in the development of a therapeutic mAb (monoclonal antibody).
We offer a comprehensive collection of recombinant Fc receptor proteins of different species (human, mouse, rat, cynomolgus, porcine) including their common variants.
Fc gamma RI / CD64 - High affinity immunoglobulin gamma Fc receptor I
Receptors that recognize the Fc portion of IgG are divided into three groups designated Fc gamma RI, RII, and RIII, also known respectively as CD64, CD32, and CD16. Fc gamma RI binds IgG with high affinity and functions during early immune responses. Fc gamma RII and RIII are low affinity receptors that recognize IgG as aggregates surrounding multivalent antigens during late immune responses. High affinity immunoglobulin gamma Fc receptor I is also known as FCGR1A, FCG1, FCGR1, CD64 and IGFR1, is a type of integral membrane glycoprotein that binds monomeric IgG-type antibodies with high affinity, which belongs to the immunoglobulin superfamily or FCGR1 family. FCGR1A / CD64 contains 3 Ig-like C2-type (immunoglobulin-like) domains. CD64 is constitutively found on only macrophages and monocytes, but treatment of polymorphonuclear leukocytes with cytokines like IFNγ and G-CSF can induce CD64 expression on these cells.
Fc gamma RIIA / CD32 - Low affinity immunoglobulin gamma Fc region receptor II
Receptors for the Fc region of IgG (Fc γ R) are members of the Ig superfamily that function in the activation or inhibition of immune responses. Three classes of human Fc γ Rs: RI (CD64), RII (CD32), and RIII (CD16), which generate multiple isoforms, are recognized. There are three genes for human Fcγ RII /CD32 (A, B, and C) and one for mouse Fcγ RII B (CD32B). CD32 is a low affinity receptor for IgG. The activating isoform, CD32A, is expressed on monocytes, neutrophils, platelets and dendritic cells. CD32A is expressed on many immune cell types (macrophage, neutrophil, eosinophils, platelets, dendritic cells and Langerhan cells), where inhibitory ITIMbearing receptors may also be coexpressed and coengaged by specific ligands. CD32A delivers an activating signal upon ligand binding, and results in the initiation of inflammatory responses including cytolysis, phagocytosis, degranulation and cytokine production. The responses can be modulated by signals from the coexpressed inhibitory receptors such as CD32B, and the strength of the signal is dependent on the ratio of expression of the activating and inhibitory receptors.
Fc gamma RIII / CD16 - Low affinity immunoglobulin gamma Fc region receptor III
CD16 is a low affinity Fc receptor, and has been identified as Fc receptors FcγRIIIa (CD16a) and FcγRIIIb (CD16b). These receptors bind to the Fc portion of IgG antibodies. CD16 encoded by two different highly homologous genes in a cell type-specific manner.CD16 is found on the surface of natural killer cells, neutrophil polymorphonuclear leukocytes, monocytes and macrophages. CD16a antigen is also known as Low affinity immunoglobulin gamma Fc region receptor III-A, Fc-gamma RIII-alpha. CD16b is a low-affinity, GPI-linked receptor expressed by neutrophils and eosinophils, whereas CD16a is an intermediate affinity polypeptide-anchored transmembrane glycoprotein expressed natural killer cells, macrophages, subpopulation of T-cells, immature thymocytes and placentaltrophoblasts.CD16a is involved in phagocytosis, secretion of enzymes and inflammatory mediators, antibodydependent cytotoxicity and clearance of immune complexes. Aberrant expression or mutations of CD16a is implicated in susceptibility to recurrent viral infections, systemic lupus erythematosus, and alloimmune neonatal neutropenia.
FcRn / FCGRT&B2M Heterodimer Protein
FCGRT & B2M heterodimer protein (FcRn complex) consist of two subunits: p51 (equivalent to FCGRT), and p14 (equivalent to beta-2-microglobulin), and forms an MHC class I-like heterodimer. Fc fragment of IgG, receptor, transporter, alpha (FCGRT) binds to the Fc region of monomeric immunoglobulins gamma and mediates the uptake of IgG from milk. FCGRT possible role in transfer of immunoglobulin G from mother to fetus. Beta-2-microglobulin (B2M) is a component of the class I major histocompatibility complex (MHC) and involved in the presentation of peptide antigens to the immune system.
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