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*
Department of Medicine, Division of Rheumatology, University of California, Los Angeles, CA 90095;
Department of Biology, Johns Hopkins University, Baltimore, MD 21205; and
Department of Medicine, University of California at San Diego, La Jolla, CA 92093
We have isolated five monoclonal IgG anti-ß2-glycoprotein-1 (anti-ß2G-1) and anti-prothrombin Fab from a patient with autoantibodies to oxidized low-density lipoproteins by phage display method. Analysis of their binding specificity revealed that all three ß2GP-1-enriched mAbs (B14, B22, B27) reacted with ß2GP-1 while both prothrombin-isolated mAbs (P11 and P13) reacted with prothrombin. Intriguingly, mAb P11 reacted with ß2GP-1 and prothrombin and showed comparable binding affinity to both Ags, with Kd values of 1.6 x 10-6 M for ß2GP-1 vs 3.2 x 10-6 M for prothrombin. This clone may thus, define a hitherto unknown shared epitope between ß2GP-1 and prothrombin. Sequence analysis of all five clones showed significant mutations of the expressed genes. One rearranged V-D-J segment was repeatedly employed by three clones (mAbs B22, B27, and P13). However, all three clones used different L chains. Of note, the pairing of VH6-D-J with the L5-Vk1 L chain in mAb P13 resulted in the loss of binding to ß2GP-1 and specific reactivity to prothrombin. Together, these data suggest that while the VH6-D-J chain may be important in the binding to ß2GP-1, pairing with certain L chains may influence this binding. These data are the first human IgG anti-ß2GP-1 and anti-prothrombin sequences reported; both represent the major subsets of antiphospholipid Abs present in antiphospholipid syndrome patients.
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