Target recognition of β2-glycoprotein I (β2GPI)-dependent anticardiolipin antibodies: Evidence for involvement of the fourth domain of β2GPI in antibody binding

Jacob George, Boris Gilburd, Maja Hojnik, Yair Levy, Pnina Langevitz, Eiji Matsuura, Takao Koike, Yehuda Shoenfeld

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

β2-glycoprotein I (β2GPI) is an absolute requirement for the binding of autoimmune anticardiolipin Abs (aCL) to cardiolipin (CL). We evaluated the target recognition of human β2GPI by IgG derived from two patients with primary and two with secondary antiphospholipid syndrome. The total IgG serum fractions and β2GPI affinity-purified IgGs were assessed by using various domain-deleted mutants (DM) of human β2GPI (DMs: I-III, I-IV, II-V, III-V, IV-V, and V) and mouse mAbs against individual β2GPI domains. The four IgGs bound slightly to CL in the absence of β2GPI and showed increased binding in the β2GPI presence. Following affinity purification of the IgGs on a β2GPI column, reactivity toward CL was absent. DMs containing domain V inhibited the binding of biotinylated β2GPI to CL. The addition to CL- coated plates of DM V, but not the other DMs, reduced the binding of all four IgGs. The anti-β2GPI IgGs bound only to complete β2GPI and DM I-IV coated on the plates. The binding to plate-adsorbed β2GPI could be inhibited by complete β2GPI and DM I-IV, the latter being a more efficient inhibitor. Further, the human anti-β2GPI IgGs could compete with the binding to β2GPI of Cof-21 mouse mAb (directed at domain IV), but not with the two other mouse mAbs. The results suggest that some 'autoimmune:' β2GPI- dependent anticardiolipin Abs recognize a β2GPI target that is distinct from the CL-binding site in domain V. The target site for some antiphospholipid syndrome IgGs appear to reside in domain IV of β2GPI.

Original languageEnglish
Pages (from-to)3917-3923
Number of pages7
JournalJournal of Immunology
Volume160
Issue number8
Publication statusPublished - Apr 15 1998
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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