Selection of nanobodies that target human neonatal Fc receptor

Sci Rep. 2013:3:1118. doi: 10.1038/srep01118. Epub 2013 Jan 23.

Abstract

FcRn is a key player in several immunological and non-immunological processes, as it mediates maternal-fetal transfer of IgG, regulates the serum persistence of IgG and albumin, and transports both ligands between different cellular compartments. In addition, FcRn enhances antigen presentation. Thus, there is an intense interest in studies of how FcRn binds and transports its cargo within and across several types of cells, and FcRn detection reagents are in high demand. Here we report on phage display-selected Nanobodies that target human FcRn. The Nanobodies were obtained from a variable-domain repertoire library isolated from a llama immunized with recombinant human FcRn. One candidate, Nb218-H4, was shown to bind FcRn with high affinity at both acidic and neutral pH, without competing ligand binding and interfering with FcRn functions, such as transcytosis of IgG. Thus, Nb218-H4 can be used as a detection probe and as a tracker for visualization of FcRn-mediated cellular transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Camelids, New World / immunology
  • Camelids, New World / metabolism
  • HEK293 Cells
  • Haplorhini
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Hydrogen-Ion Concentration
  • Immunoglobulin G / immunology
  • Ligands
  • Mice
  • Rats
  • Receptors, Fc / immunology*
  • Receptors, Fc / metabolism*
  • Single-Domain Antibodies / immunology*
  • Single-Domain Antibodies / metabolism*
  • Swine
  • Transcytosis / immunology

Substances

  • Histocompatibility Antigens Class I
  • Immunoglobulin G
  • Ligands
  • Receptors, Fc
  • Single-Domain Antibodies
  • Fc receptor, neonatal