Abstract Molecular interactions between therapeutic antibodies and neonatal Fc receptor (FcRn) are major contributors to the long serum half-life of antibodies. Therefore, the in vitro affinity of IgG for FcRn is an important indicator of in vivo pharmacokinetic properties. However, the molecular basis of IgG-FcRn interactions is not fully understood from experimental and structural perspectives. Affinity evaluation using surface plasmon resonance is difficult. The molecular mechanism by which domains other than Fc or surface charges affect FcRn binding remains unclear. In this study, we developed an engineered FcRn-immobilized column for affinity chromatography. We analyzed various types of antibodies to link physicochemical characteristics and FcRn affinity. Furthermore, analysis using charge-engineered mutants indicated that the lateral surface of L chain also affects the FcRn affinity. Finally, we presented a structural model of the IgG-FcRn complex to discuss the molecular mechanism of how the charges at L chain affect the FcRn affinity.
Kiyoshi et al. (Tue,) studied this question.