Epitope specificity of monoclonal anti- beta sub(2)-glycoprotein I antibodies derived from patients with the antiphospholipid syndrome

• Published in: The Journal of immunology (1950) Vol. 155; no. 3; pp. 1629 - 1636
• Main Authors: Wang, Min-Xia, Kandiah, DA, Ichikawa, K, Khamashta, M, Hughes, G, Koike, T, Roubey, R, Krilis, SA
• Format: Journal Article
• Language: English
• Published: 01-01-1995
• ISSN: 0022-1767

beta sub(2)-Glycoprotein I ( beta sub(2)-GPI) has been identified as a cofactor in the recognition of the phospholipid Ag cardiolipin (CL) by anticardiolipin Ab (aCL) purified from patients with autoimmune diseases. However, there is considerable controversy as to the exact nature of the epitopes to which these Abs are directed. mAb derived from patients with the antiphospholipid syndrome bound to CL only in the presence of beta sub(2)GPI. Synthetic peptides that span the fifth C-terminal domain of beta sub(2)GPI supported the binding of one of the mAbs to CL in a beta sub(2)GPI-free system. These peptides possessed the phospholipid binding sequence Cys super(281)-Lys-Asn-Lys-Glu-Lys-Lys-Cys super(288). Three of the mAbs bound to beta sub(2)GPI that had been adsorbed on gamma -irradiated microtiter plates. Binding to beta sub(2)GPI was inhibited in a dose-dependent manner by the peptides from the carboxyl-terminal end of beta sub(2)GPI and soluble beta sub(2)GPI, indicating that the mAb bound to peptides and beta sub(2)GPI in free solution. Thus, mAbs derived from patients with the antiphospholipid syndrome have specificity for epitopes on the fifth domain of beta sub(2)GPI. Our results support the idea that beta sub(2)GPI acts as a primary Ag for these Abs.