FcRn Antikörper

The neonatal Fc receptor (FnRn) owes its name to being the receptor that transports maternal IgG from mother to lactating neonatal offspring and for being identified first in the intestine of neonatal rats as the receptor responsible for the transport of IgG from the lumen to the circulation. However, FcRn functions are far more universal, and it is virtually ubiquitously expressed.

FcRn is considered a non-classical Fc receptor for IgG (FcγR). It is structurally related to major histocompatibility class I (MHC-I) family and it associates with beta-2-microglobulin (β₂m). On the other hand, it does not present antigenic peptides to T cells and. It has also a second interaction partner, albumin, that is not involved in the body’s immune response. FcRn prevents intracellular degradation of IgG and albumin and extends their half-life considerable, making them the two most abundant serum proteins.

Because of its interaction with IgG and albumin, FcRn has become a high-interest therapeutic target. For one, it can be exploited to extend the half-life of therapeutic antibodies and IgG- or albumin-fused proteins. Mutations of amino acids influencing the pH dependency of IgG and albumin binding can be mutated to achieve the desired effect. Binding of IgG to FcRn also offers the possibility to enhance their clearance. Autoantibodies that recognized self-antigens are the cause of certain autoimmune diseases. By engineering competing antibodies that bind tighter to FcRn and effectively block the receptor increase clearance of the disease-causing antibodies. Lastly, the FcRn enhances the transport of therapeutic IgG fc or albumin fusion-protein across mucosal membranes, thus facilitating distribution and improving their absorption.

Anti-FcRn antibodies are essential tools to elucidate the biological function of FcRn under normal circumstances and in pathologies such as autoimmune disease and cancer. They enable FcRn imaging in tissue using IHC or IF and quantitation through FACS. As blocking reagents they are useful to identify epitopes on FcRn targeted by antibody-based drugs or albumin-conjugated therapeutics. They can also use autoantibody recycling and influence the half-life of therapeutic antibodies.

Albumin and IgG Binding to the FcRn Heterodimer