Binding affinities of human IgG1 and chimerized pig and rabbit derivatives to human, pig and rabbit Fc gamma receptor IIIA

PLoS One. 2019 Jul 19;14(7):e0219999. doi: 10.1371/journal.pone.0219999. eCollection 2019.

Abstract

While pigs and rabbits are used as models for human immune diseases, FcγR binding is poorly characterized in both test species. To evaluate antibody binding to FcγRIIIA, a receptor involved in antibody-dependent cellular cytotoxicity, chimerized antibodies were generated by grafting the variable regions of a human IgG1 onto scaffolds from both species. The affinities of the parent and chimeric antibodies to the FcγRIIIA proteins from all three species were determined. While the human IgG1 and rabbit IgG had similar affinities for each FcγRIIIA with notable differences across species, pig IgG1 only bound pig FcγRIIIA with appreciable affinity. Also, the functional pig and rabbit proteins described here can be used in future experiments, such as pharmacology and mechanism of action studies.

MeSH terms

  • Animals
  • Antibody Affinity / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression
  • Humans
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / isolation & purification
  • Immunoglobulin G / metabolism*
  • Protein Binding
  • Rabbits
  • Receptors, IgG / genetics
  • Receptors, IgG / isolation & purification
  • Receptors, IgG / metabolism*
  • Recombinant Fusion Proteins*
  • Surface Plasmon Resonance
  • Swine

Substances

  • Immunoglobulin G
  • Receptors, IgG
  • Recombinant Fusion Proteins

Grants and funding

Iconic Therapeutics provided support in the form of salaries for authors MMB, AGC and JWT but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the author contributions section.