Study on the specificity and thrombogenicproperty of anficardiolipin antibodies in serafrom patients with the antiphospholipid syndrome.

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1) Nine clones of IgM monoclonal beta2-glycoprotein I (beta2-GPI) dependent anticardiolipin antibodies (aCL) were established from peripheral blood lymphocytes. These monoclonal aCL recognized beta2-GPI structurally altered by binding to anionic phospholipids.2) Reactivity of monoclonal aCL derived from patients with the APS and from APS prone mice with domain deleted mutants of beta2-GPI.Most of monoclonal aCL were considered to recognize epitope (s) related to 4th domain of beta2-GPI.3) Three dimensional structure of human beta2-GPI was analogized from the tertial structure of the Factor H,using GENETYX-SV/R and QUANTA/CHARMm, which were developed to analyze tertial structure of peptides and proteins.4) To identify the epitopes recognized by pathogenic aCL,random peptide libraries were searched with monoclonal antibodies against beta2-GPI.Peptides bound to EY1C8 and EY2C9, human monoclonal aCL,had consensus motifs respectively. Peptides reacted with WBCAL-1, a mouse monoclonal anti-human beta2-GPI antibody, had overlapping consesus sequences.5)To clarify the epitope recognized by monoclonal antibody aganist beta2-GPI,tertial structure model of human beta2-GPI was searched for structures similar to the identified motifs. The putative epitope recognized by EY1C8 and EY2C9 were identified on the 4th domain of beta2-GPI.The epitope was covered by 3rd domain in free from beta2-GPI.The epitope recognized by Cof-18 was near the phospholipid binding site on the 5th domain of beta2-GPI.This may explain the inhibition of the binding of beta2-GPI to anionic phospholipids by Cof-18.