Selection of nanobodies that target human neonatal Fc receptor.
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.
Centre for Immune Regulation (CIR) and Department of Molecular Biosciences, University of Oslo, Oslo, Norway. j.t.andersen@imbv.uio.no
Jan Terje
JT
Andersen
Maria
M
Gonzalez-Pajuelo
Stian
S
Foss
Ole J B
OJ
Landsverk
Débora
D
Pinto
Alexander
A
Szyroki
Hans J
HJ
de Haard
Michael
M
Saunders
Peter
P
Vanlandschoot
Inger
I
Sandlie
D000818:Animals; D001692:Biological Transport; D002161:Camelids, New World / Q000276:immunology / Q000378:metabolism; D057809:HEK293 Cells; D000882:Haplorhini; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000276:immunology; D008024:Ligands; D051379:Mice; D051381:Rats; D011961:Receptors, Fc / Q000276:immunology* / Q000378:metabolism*; D061905:Single-Domain Antibodies / Q000276:immunology* / Q000378:metabolism*; D013552:Swine; D057900:Transcytosis / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D008024:Ligands; D011961:Receptors, Fc; D061905:Single-Domain Antibodies; C100688:Fc receptor, neonatal