IDENTIFICATION OF CRITICAL IGG BINDING EPITOPES ON THE NEONATAL FC RECEPTOR

The neonatal Fc receptor (FcRn) binds maternal immunoglobulin G (IgG) during the acquisition of passive immunity by the fetus or newborn. Fc Rn also binds IgG and returns it to the bloodstream, thus protecting I gG from a default degradative pathway. Biosensor assays have been used to characterize the interaction of a soluble form of rat FcRn with Ig G, and demonstrate that FcRn dimerization and immobilization are neces sary to reproduce in vivo binding characteristics. Here, we report the identification of several FcRn amino acid substitutions that disrupt its affinity for IgG and examine the effect of alteration of residues at the FcRn dimer interface. The role of these amino acids is discusse d in the context of the previously reported structures of rat FcRn and a complex of FcRn with the Fc portion of IgG. (C) 1997 Academic Press Limited.