title: Identification of critical IgG binding epitopes on the neonatal Fc receptor.
abstract: The neonatal Fc receptor (FcRn) binds maternal immunoglobulin G (IgG) during the acquisition of passive immunity by the fetus or newborn. FcRn also binds IgG and returns it to the bloodstream, thus protecting IgG from a default degradative pathway. Biosensor assays have been used to characterize the interaction of a soluble form of rat FcRn with IgG, and demonstrate that FcRn dimerization and immobilization are necessary 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 discussed in the context of the previously reported structures of rat FcRn and a complex of FcRn with the Fc portion of IgG.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena 91125, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Vaughn
authors.forename: C M
authors.initials: CM
authors.lastname: Milburn
authors.forename: D M
authors.initials: DM
authors.lastname: Penny
authors.forename: W L
authors.initials: WL
authors.lastname: Martin
authors.forename: J L
authors.initials: JL
authors.lastname: Johnson
authors.forename: P J
authors.initials: PJ
authors.lastname: Bjorkman
mesh_terms: D000818:Animals; D015374:Biosensing Techniques; D019281:Dimerization; D000939:Epitopes / Q000737:chemistry* / Q000378:metabolism*; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D051381:Rats; D011961:Receptors, Fc / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D000939:Epitopes; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011961:Receptors, Fc; D011994:Recombinant Proteins