EPITOPE SPECIFICITY OF MONOCLONAL ANTI-BETA(2)-GLYCOPROTEIN-I ANTIBODIES DERIVED FROM PATIENTS WITH THE ANTIPHOSPHOLIPID SYNDROME

beta(2)-Glycoprotein I (beta(2)GPI) has been identified as a cofactor in the recognition of the phospholipid Ag cardiolipin (CL) by anticard iolipin Ab (aCL) purified from patients with autoimmune diseases. Howe ver, there is considerable controversy as to the exact nature of the e pitopes to which these Abs are directed. mAb derived from patients wit h the antiphospholipid syndrome bound to CL only in the presence of be ta(2)GPI. Synthetic peptides that span the fifth C-terminal domain of beta(2)GPI supported the binding of one of the mAbs to CC in a beta(2) GPI-free system. These peptides possessed the phospholipid binding seq uence Cys(281)-Lys-Asn-Lys-Glu-Lys-Lys-Cys(288). Three of the mAbs bou nd to beta(2)GPI that had been adsorbed on gamma-irradiated microtiter plates. Binding to beta(2)GPI was inhibited in a dose-dependent manne r by the peptides from the carboxyl-terminal end of beta(2)GPI and sol uble beta(2)GPI, indicating that the mAb bound to peptides and beta(2) GPI in free solution. Thus, mAbs derived from patients with the antiph ospholipid syndrome have specificity for epitopes on the fifth domain of beta(2)GPI. Our results support the idea that beta(2)GPI acts as a primary Ag for these Abs.