The R2 of the curve of the current change rate of the seven IgGs was measured in the corresponding concentration range beyond 95%, which showed that the action of the seven IgGs and hFcRn conformed to the hyperbolic law. was similar to the catalytic kinetics of enzyme and substrate, and there was a ligand-receptor saturation effect. The order of the interconnect allosteric constants (Ka), which is similar to the Michaelis constant (Km), was human IgG < bovine IgG < horse IgG < rabbit IgG < sheep IgG < donkey IgG < quail IgY. The results showed that hFcRn had the strongest ability to transport human IgG, IQGAP2 which was consistent with the evolution of the system. Therefore, our 2-Keto Crizotinib hFcRn electrochemical receptor sensor can be used to measure and evaluate the interconnected allosteric network. It is also an essential parameter of the interaction between hFcRn and different IgGs and, thus, provides a new detection and evaluation method for immunoemulsion, therapeutic monoclonal antibody therapy, heteroantibody treatment, and half-life research. Keywords: -immunoglobulin (IgG), neonatal IgG Fc receptor (FcRn), human FcRn (hFcRn) electrochemical receptor sensor, interconnected allosteric constants (Ka) 1. Introduction The neonatal immunoglobulin (IgG) Fc receptor (FcRn) is composed of a heavy chain -chain with a molecular weight of about 50 kD and a light chain 2-microglobulin (2m) with a molecular weight of about 15 kD. Its structure is similar to the heterodimer receptor of the major histocompatibility complex (MHC) class I molecule [1], while its main function is to mediate the non-specific endocytosis of IgG from pregnant and lactating mothers, which is transported to the fetus via the placenta barrier or to infants via the breast barrier and intestinal wall barrier so that pregnant and lactating mothers can transmit humoral immunity to offspring [2,3,4], as well as resist congenital diseases such as hypoproteinemia [5,6]. In addition, FcRn is also a single receptor for IgG and albumin [7,8]. It binds to IgG/albumin in a pH-dependent manner (at acidic pH (pH 6.5) with a nanomolar affinity at a neutral pH or higher (pH 7.0) not combined or released) [9,10,11,12], so that IgG/albumin is internalized into the acidic endosome membrane where FcRn is located by nonspecific endocytosis, which is free from degradation due to dissociation from lysosomal fate (Figure 1), thus ensuring the long half-life of IgG and albumin in vivo [13,14,15]. Open in a separate window Figure 1 Fc receptor (FcRn)-mediated immunoglobulin G (IgG) transfer in the human body. FcRn in intracellular vesicles allows 2-Keto Crizotinib IgG to enter the cell through non-specific liquid endocytosis, and then internalizes in an acidic environment where the endosome of FcRn is bound to FcRn. After that, under the action of physiological pH, FcRn transports IgG out of the cells and reaches the innate immune cells containing FcRS to play out the immune role through the blood. The two functions of FcRn are mainly achieved through the interaction of multiple amino acid residues (such as tryptophan 131, glutamate 116, isoleucine 11, etc.) in 1 and 2 domains with CH2-CH3 amino acid residues (such as 2-Keto Crizotinib isoleucine 253, histidine 310 and histidine 435) in IgG Fc domains [3,13]. When IgG is released into the blood, IgG continues to bind to Fc receptors (FcRs), because FcRs of IgG are widely expressed in macrophages, monocytes, neutrophils, basophils, natural killer (NK) cells and other immune cells [16]. Therefore, when the antigen binds to the Fab end of IgG, FcRs generate positive or negative intracellular signals regulating cell response [17]. Some of the effector cells internalize the soluble immune complex or cell-antibody complex through endocytosis, and other effector cells kill the target cells through antibody-dependent cell-mediated cytotoxicity (ADCC) [18], which has great potential in the treatment of many diseases and even tumors by using therapeutic monoclonal 2-Keto Crizotinib antibodies. For instance, vaccinating pregnant women with influenza vaccine reduces the probability of infants to suffering from influenza and mothers to suffering from respiratory diseases [19,20]. Fc-insulin-encapsulated nanoparticles are used to target the intestinal mucosal transport of wild-type mice so as to render the wild-type mice in a long-term hypoglycemic state [21,22]. Generally, the function of the therapeutic monoclonal antibody is primarily determined by the interaction between the Fc 2-Keto Crizotinib domain of the antibody and the FcRs [23]. Therefore, quantitative evaluation of this interaction is essential for solving the half-life of therapeutic monoclonal antibodies however, only a few studies addressed this issue thus far. Because the heterologous IgG can be transmitted to the blood circulation of the body through the intestinal mucosa and can be combined with various leukocytes with Fc receptor in the blood, it provides a theoretical basis for the passive immune function of milk. Substantial evidence has shown that the milk of.