Proteolytic cleavage of β2-glycoprotein I: Reduction of antigenicity and the structural relationship

Eiji Matsuura, Junko Inagaki, Hideki Kasahara, Daisuke Yamamoto, Tatsuya Atsumi, Kazuko Kobayashi, Keiko Kaihara, Dandan Zhao, Kenji Ichikawa, Akito Tsutsumi, Tatsuji Yasuda, Douglas A. Triplett, Takao Koike

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32 Citations (Scopus)

Abstract

Binding of β2-glycoprotein I (β2-GPI)-dependent anticardiolipin antibodies (aCL) derived from antiphospholipid syndrome (APS) is significantly reduced in aCL ELISA due to loss of the phospholipid (PL) binding property of β2-GPI by plasmin treatment. In the present study, the treatment generated a nicked form of β2-GPI and resulted in loss of antigenicity for the autoantibodies detected in ELISA, using an β2-GPI directly adsorbed polyoxygenated carboxylated plate, the assay system of which was not related to PL binding. The nicked form bound to neither Cu2+-oxidized low-density lipoprotein (oxLDL) nor to β2-GPI-specific lipid ligands isolated from oxLDL, the result being a complete loss of subsequent binding of anti-β2-GPI autoantibodies. The conformational change in the nicked domain V was predicted from its intact structure determined by an X-ray analysis (implemented in Protein Data Bank: 1C1Z), molecular modeling and epitope mapping of a monoclonal anti-β2-GPI antibody, i.e. Cof-18, which recognizes the related structure. The analysis revealed that novel hydrophobic and electrostatic interactions appeared in domain V after the cleavage, thereby affecting the PL binding of β2-GPI. Such a conformational change may have important implications for exposure of cryptic epitopes located in the domains such as domain IV.

Original languageEnglish
Pages (from-to)1183-1192
Number of pages10
JournalInternational Immunology
Volume12
Issue number8
DOIs
Publication statusPublished - Jan 1 2000

Keywords

  • Anti-β-glycoprotein I antibodies
  • Antiphospholipid syndrome
  • Epitope mapping
  • Plasmin
  • Structure

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Matsuura, E., Inagaki, J., Kasahara, H., Yamamoto, D., Atsumi, T., Kobayashi, K., Kaihara, K., Zhao, D., Ichikawa, K., Tsutsumi, A., Yasuda, T., Triplett, D. A., & Koike, T. (2000). Proteolytic cleavage of β2-glycoprotein I: Reduction of antigenicity and the structural relationship. International Immunology, 12(8), 1183-1192. https://doi.org/10.1093/intimm/12.8.1183