title: Monoclonal antibodies directed against human FcRn and their applications.
abstract: The MHC class I-like Fc receptor (FcRn) is an intracellular trafficking Fc receptor that is uniquely responsible for the extended serum half-life of antibodies of the IgG subclass and their ability to transport across cellular barriers. By performing these functions, FcRn affects numerous facets of antibody biology and pathobiology. Its critical role in controlling IgG pharmacokinetics has been leveraged for the design of therapeutic antibodies and related biologics. FcRn also traffics serum albumin and is responsible for the enhanced pharmacokinetic properties of albumin-conjugated therapeutics. The understanding of FcRn and its therapeutic applications has been limited by a paucity of reliable serological reagents against human FcRn. Here, we describe the properties of a new panel of highly specific monoclonal antibodies (mAbs) directed against human FcRn with diverse epitope specificities. We show that this antibody panel can be used to study the tissue expression pattern of human FcRn, to selectively block IgG and serum albumin binding to human FcRn in vitro and to inhibit FcRn function in vivo. This mAb panel provides a powerful resource for probing the biology of human FcRn and for the evaluation of therapeutic FcRn blockade strategies.
authors.affiliation: The Jackson Laboratory; Bar Harbor, ME USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Christianson
authors.affiliation: The Jackson Laboratory; Bar Harbor, ME USA.
authors.forename: Victor Z
authors.initials: VZ
authors.lastname: Sun
authors.affiliation: The Jackson Laboratory; Bar Harbor, ME USA; Current address: Barnes-Jewish Hospital; St. Louis, MO USA.
authors.forename: Shreeram
authors.initials: S
authors.lastname: Akilesh
authors.affiliation: The Jackson Laboratory; Bar Harbor, ME USA; Current address: VIB Department of Molecular and Cellular Interactions; Laboratory for Cellular and Molecular Immunology; Vrije Universiteit; Brussels, Belgium.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Pesavento
authors.affiliation: The Jackson Laboratory; Bar Harbor, ME USA.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Proetzel
authors.affiliation: The Jackson Laboratory; Bar Harbor, ME USA.
authors.forename: Derry C
authors.initials: DC
authors.lastname: Roopenian
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology / Q000494:pharmacology; D000918:Antibody Specificity; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D011961:Receptors, Fc / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D012709:Serum Albumin / Q000276:immunology / Q000378:metabolism
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; D012709:Serum Albumin; C100688:Fc receptor, neonatal