Development of new models for the analysis of Fc-FcRn interactions.
An important question remains as to which FcRn binding parameters, if any, correlate with the serum half-life of antibodies. In the present study, we used a BIACore surface plasmon resonance (SPR) device to study kinetic properties of antibody binding to FcRn at different pHs and under different binding reaction conditions. The ability of many different models to fit the data was tested. The previous models could not adequately explain all of the data collected. We now present models that have intuitive appeal and fit a broader range of data than previous models. Specifically, the model assumes that there are two forms of FcRn on the BIAcore chip and that, in addition to monomeric IgG, there is some aggregated IgG that can function as ligand. Although this model represents an improvement over previous models, it is still not globally valid for the entire range of data that was collected. Even with these limitations, the model provides a powerful new tool to analyze not only FcRn-IgG interactions but also other complex protein-protein interactions.
Gurbaxani
Brian Mohan
BM
Department of Microbiology, Immunology and Molecular Genetics and The Molecular Biology Institute, University of California, Los Angeles, CA 90049, USA. buw8@cdc.gov
Morrison
Sherie L
SL
D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D006207:Half-Life; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D018448:Models, Immunological; D011961:Receptors, Fc / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020349:Surface Plasmon Resonance
D015395:Histocompatibility Antigens Class I; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; C100688:Fc receptor, neonatal