AMINO-ACID-SEQUENCE OF THE REGION OF BETA-2-GLYCOPROTEIN 1 (GP1) WHICH MEDIATES BINDING OF AUTOANTIBODIES TO THE CARDIOLIPIN-GP1 COMPLEX INHUMANS

Anticardiolipin antibodies (ACA) in sera from patients with autoimmune and infectious diseases were tested for binding to beta2-glycoprotein 1 (gp 1) in order to determine whether human gp 1 acts as a cofactor for the binding of ACA to cardiolipin (CL) or as an antigen recognized by ACA. While none of the ACA-positive sera tested recognized gp 1 by itself, gp 1 was necessary for the binding of ACA to CL in sera from four patients with autoimmune diseases. In three of the four sera the presence of lupus anticoagulant (LA) was detected by prolonged partial thromboplastin time (PTT). Examinations using the bovine equivalent o f human gp 1 contained in fetal calf serum (FCS) and adult bovine seru m (ABS) showed that the human protein can be replaced by the bovine eq uivalent in the enzyme-linked immunosorbent assay (ELISA). Using affin ity-purified antibodies directed against the CL-gp 1 complex it was sh own that the binding of these antibodies is dependent on the concentra tion of the bovine gp1 equivalent contained in the formed complex. Sim iliar results found with the human gp 1 confirmed this assertion. In o rder to find out which region of gp1 might mediate the binding between ACA and cardiolipin, we examined to what extent selected oligopeptide sequences of gp 1 can substitute for the protein. Peptide P2 (represe nting the amino acids at positions 268-278 of the gp 1 molecule) and g p 1 showed about the same binding capacity. Histidine in this peptide seems to be essential for the binding to CL as we found decreased bind ing with peptides modified in this position. Conclusions from this wor k show that gp 1 does not act as a relevant antigen for ACA, but occup ies an essential function in the complex formed with cardiolipin for a certain group of ACA.