Two conformational forms of target-bound iC3b that distinctively bind complement receptors 1 and 2 and two specific monoclonal antibodies

  • Ulf R. Nilsson Division of Clinical Immunology, Rudbeck Laboratory C5, Uppsala University, Sweden
  • Lillemor Funke Division of Clinical Immunology, Rudbeck Laboratory C5, Uppsala University, Sweden
  • Bo Nilsson Division of Clinical Immunology, Rudbeck Laboratory C5, Uppsala University, Sweden
  • Kristina N. Ekdahl Division of Clinical Immunology, Rudbeck Laboratory C5, Uppsala University, Sweden; and Department of Natural Sciences, Linneaus University, Kalmar, Sweden
Keywords: Complement C3, complement receptors, immunoglobulin G (IgG), monoclonal antibodies, neo-epitopes

Abstract

Introduction. The complement system is an essential part of the immune system of vertebrates. The central event of the complement activation cascade is the sequential proteolytic activation of C3, which is associated with profound alterations in the molecule's structure and conformation and is responsible for triggering most of the biological effects of complement.

Material and methods. Here, we have studied the conformation of C3 fragments deposited onto an IgG-coated surface from human serum during complement activation, using a set of unique monoclonal antibodies (mAbs) that are all specific for the C3dg portion of bound iC3b.

Results. We were able to identify two conformational forms of target-bound iC3b: the first recognized by mAb 7D18.1, and the second by mAb 7D323.1. The first species of iC3b bound recombinant complement receptor 1 (CR1), while the second bound CR2. Since CR1 and CR2 are expressed by different subsets of leukocytes, this difference in receptor-binding capacity implies that there is a biological difference between the two forms of surface-bound iC3b.

Conclusion. We propose that mAbs 7D18.1 and 7D323.1 can act as surrogate markers for CR1 and CR2, respectively, and that they may be useful tools for studying the immune complexes that are generated in various autoimmune diseases.

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Published
2010-11-11
How to Cite
Nilsson U. R., Funke L., Nilsson B., & Ekdahl K. N. (2010). Two conformational forms of target-bound iC3b that distinctively bind complement receptors 1 and 2 and two specific monoclonal antibodies. Upsala Journal of Medical Sciences, 116(1), 26–33. https://doi.org/10.3109/03009734.2010.528465
Section
Original Articles