Abstract
Neonatal γ-immunoglobulin (IgG) Fc receptor (FcγRn) is a receptor that transports IgG across the intestinal mucosa, placenta, and mammary gland, ensuring the balance of IgG and albumin in the body. These functions of FcγRn depend on the intracellular signal transduction and activation caused by the combination of its extracellular domain and IgG Fc domain. Nevertheless, there are still no kinetic studies on this interaction. Consequently, in the present study, we successfully constructed the human FcγRn (hFcγRn) electrochemical receptor sensor. The signal amplification system formed by chitosan nanogold-hFcγRn protein and horseradish peroxidase was used to simulate the cell signal amplification system in vivo, and the kinetic effects between seven IgG and hFcγRn receptors from different species were quantitatively measured. The results showed that the interaction of these seven IgGs with hFcγRn 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 hFcγRn had the strongest ability to transport human IgG, which was consistent with the evolution of the system. Therefore, our hFcγRn electrochemical receptor sensor can be used to measure and evaluate the interconnected allosteric network. It is also an essential parameter of the interaction between hFcγRn and different IgGs and, thus, provides a new detection and evaluation method for immunoemulsion, therapeutic monoclonal antibody therapy, heteroantibody treatment, and half-life research.
Highlights
The neonatal immunoglobulin (IgG) Fc receptor (FcγRn) is composed of a heavy chain α-chain with a molecular weight of about 50 kD and a light chain β2 -microglobulin (β2 m) 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 immunoglobulin G (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]
FcγRn is a single receptor for IgG and albumin [7,8]. It binds to IgG/albumin in a pH-dependent manner (at acidic pH with a nanomolar affinity at a neutral pH or higher not combined or released) [9,10,11,12], so that IgG/albumin is internalized into the acidic endosome membrane where FcγRn is located by nonspecific endocytosis, which is free
Summary
The neonatal immunoglobulin (IgG) Fc receptor (FcγRn) is composed of a heavy chain α-chain with a molecular weight of about 50 kD and a light chain β2 -microglobulin (β2 m) with a molecular weight of about 15 kD. FcγRn is 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 FcγRn is located by nonspecific endocytosis, which is free. IgG/albumin is internalized into the acidic endosome membrane where FcγRn is located by from degradation due to dissociation from lysosomal fate
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