Research Article Open Access

IgG Subclass Variation of a Monoclonal Antibody Binding to Human Fc-Gamma Receptors

Rekha Patel1, Krista K. Johnson1, Bruce A. Andrien1 and Paul P. Tamburini1
  • 1 Alexion Pharmaceuticals Inc, United States

Abstract

The importance of human Fc receptors in immune regulation is well known. Their role is critical not only in the recruitment of cellular effector functions but also in regulating the balance in the periphery between autoimmunity and tolerance. Despite their central importance, there is a dearth of literature on controlled numeric comparisons in affinities of antibody subclasses for gamma receptors. To date, no studies have directly compared humanized antibodies with the same variable region and differing Fc region subclasses which would rule out any differences that may be attributed to variations in the variable region. In this study we characterized the interaction between four humanized monoclonal antibodies; IgG1, G2, G3 and G4, each possessing an identical variable region and the repertoire of human Fc-gamma (Fcγ) receptors (FcγRI, FcγRIIA, FcγRIIB, FcγRIIIA and FcγRIIIB). The studies were performed using both Surface Plasmon Resonance (SPR) and Enzyme-Linked Immunosorbent-Assay (ELISA) formats. The affinities of the antibodies for their antigen molecule, an endogenous human protein, were also analyzed by SPR. While the identity of the Fc-region had no significant effect on the binding to antigen, substantially different affinities for each of the Fcγ receptors, FcγRI, FcγRIIA, FcγRIIB, FcγRIIIA and FcγRIIIB were observed across the various Fc-subclasses.

American Journal of Biochemistry and Biotechnology
Volume 9 No. 3, 2013, 206-218

DOI: https://doi.org/10.3844/ajbbsp.2013.206.218

Submitted On: 6 January 2012 Published On: 21 September 2013

How to Cite: Patel, R., Johnson, K. K., Andrien, B. A. & Tamburini, P. P. (2013). IgG Subclass Variation of a Monoclonal Antibody Binding to Human Fc-Gamma Receptors. American Journal of Biochemistry and Biotechnology, 9(3), 206-218. https://doi.org/10.3844/ajbbsp.2013.206.218

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Keywords

  • FC-Gamma Receptors
  • Surface Plasmon Resonance (SPR)
  • Monoclonal Antibodies
  • IgG Subclass
  • Affinity
  • ELISA