I don’t know the appropriate translation for the Chinese and English text, so I’ve pasted the original text to avoid misleading. As long as you understand it, if you have a suitable translation, please comment in the comment area. Original link: https://ashpublications.org/blood/article/113/16/3716/25117/Specificity-and-affinity-of-human-Fc-receptors-and
1. Summary
Different genes encode 6 types of human Among IgG receptors (hFcγRs), three receptors have two or three polymorphisms. The specificity and affinity of these receptors with various IgG subtypes are not yet clear (this is an article from 2009, and no one may have done a systematic comparison before 2009). This information is crucial for antibody-based immunotherapies, which are increasingly being used clinically. The authors studied the binding of polyclonal antibodies of IgG1, IgG2, IgG3, and IgG4 and the monoclonal antibody to FcγRI, FcγRIIA, FcγRIIB, FcγRIIC, FcγRIIIA, FcγRIIIB, and their polymorphic structures. Wild-type and hypofucosylated monoclonal antibodies against CD20 and RhD were also tested. The authors found that IgG1 and IgG3 can bind to all types of Fc receptors used; IgG2 cannot bind to FcγRIIA-H131, and can also bind to FcγRIIA-R131 and FcγRIIA-V158 with low affinity; IgG4 binds to FcγRI, FcγRIIA, FcγRIIB, FcγRIIC, FcγRIIIA- V158. The affinity of the inhibitory receptor FcγRIIB to IgG1, IgG2, and IgG3 is lower than that of other receptors. We also identified parameters that determine the specificity and affinity of hFcγRs for IgG subclasses. These results demonstrate that the specificity and affinity of hFcγR correspond to the biological activity of the antibody. Therefore, these results highlight the role of Fc receptors in the therapeutic and therapeutic effects that occur with antibody therapy.
2. Introduction
The biological activity of antibodies depends on the interaction between their Fc structure and the effector system. These are essentially complements and cells. Antibodies bind to Fc receptor cells. Fc receptors can be adapted to all types of antibodies. These receptors are expressed on a wide variety of cell types and serve different biological functions, and they exert regulatory functions when they form complexes with antibodies. Most cells express different Fc receptors, and because the intracellular regions of these receptors are different, different types of Fc receptors will trigger different signaling pathways in cells. Activated receptors possess immunoreceptor tyrosine activation motifs (ITAMs). ITAMs are present in the intracytoplasmic structure of FcRγ, a homologous common subunit that associates with the ligand-binding subunit of most activated FcRs. ITAMs are also present in the intracytoplasmic domains of 2 single-chain activating receptors. Inhibitory FcRs are single-chain receptors that possess an immunoreceptor tyrosine-based inhibitory motif (ITIM) in their intracellular domain. Other FcRs are inserted into the outer layer of the plasma membrane through a glycosylphosphatidylinositol (GPI) anchor and do not contain any signaling motifs. FcRs are associated with many antibody-dependent diseases and are key molecules for antibody-based immunotherapy. For example, these include the treatment of non-Hodgkin lymphoma with a mouse/human chimeric IgG1 anti-D20 antibody, and the prevention of hemolytic disease of the newborn with a mixture of anti-RHD IgG1 and IgG3 polyclonal antibodies. However, therapeutic antibodies also have potential harms, as exemplified by a recent clinical trial using an IgG4 anti-CD28 antibody. The four human IgG subtypes are produced in varying amounts in response to the various antigens . T-dependent protein antigens mainly elicit IgG1 and IgG3 antibodies, while T-independent carbohydrate antigens mainly elicit IgG2 antibodies. Chronic antigenic stimulation, such as allergic desensitization, can induce IgG4 antibodies. The biological activity of each IgG subtype is unknown. IgG receptors (FcγRs) are surprisingly abundant in humans. They include high-affinity and low-affinity receptors. Both high-affinity and low-affinity FcγRs bind IgG-immune complexes with high affinity, but only high-affinity FcγRs can bind monomeric IgG. Humans have one high-affinity IgG receptor, hFcγRI (CD64), and two low-affinity IgG receptor families, hFcγRIIA, IIB, and IIC (CD32), and hFcγRIIIA and IIIB (CD16). hFcγRI and hFcγRIIIA are activating receptors related to FcR, hFcγRIIA and hFcγRIIC are single-chain activating receptors, hFcγRIIB is a single-chain inhibitory receptor, and hFcγRIIIB is a GPI-anchored receptor, whose functions are not yet clear.
The multiplicity of hFcγRs is further increased by a series of polymorphisms in their extracellular domains. The two alleles of the gene encoding hFcγRIIA produced 2 variants that differed at position 131, named low responder (H131) and high responder (R131). H131 and R131 alleles have different distributions in whites, Japanese, and Chinese. The two alleles of the gene encoding hFcγRIIIA produce 2 different variants at position 158 (V158 and F158). Two alleles of the gene encoding hFcγRIIIB produce 2 variants differing at 4 positions, NA1 (R36 N65 D82 V106) and NA2 (S36 S65 N82 I106), which have different glycosylated patterns. Furthermore, duplication of the gene encoding hFcγRIIIB may produce different numbers of gene copies in different individuals. A single individual may therefore express all 3 hFcγRIIIB variants. hFcγR polymorphisms are associated with autoimmune and infectious diseases. hFcγRIIA-R131 is associated with increased prevalence of kidney disease, bacterial infections, and possibly systemic lupus erythematosus (SLE). hFcγRIIIA-F158 is associated with systemic lupus erythematosus and rheumatoid arthritis (RA). I'm too lazy to copy the rest of
. It's in my Jianshu account, https://www.jianshu.com/p/e7652640825b
