THE GLYCOPROTEIN-IB-IX COMPLEX-SPECIFIC MONOCLONAL-ANTIBODY SZ1 BINDSTO A CONFORMATION-SENSITIVE EPITOPE ON GLYCOPROTEIN-IX - IMPLICATIONSFOR THE TARGET ANTIGEN OF QUININE QUINIDINE-DEPENDENT AUTOANTIBODIES/

The monoclonal antibody SZ1 is of interest for two reasons: it was use d to define complex formation between glycoprotein (GP) Ib and GP IX, and its epitope is likely to be identical to that recognized by most q uinine- and quinidine-dependent autoantibodies that cause thrombocytop enia. To determine the location of the epitope for SZ1 within the GP I b-IX complex (which consists of three subunits: GP Ib alpha, GP Ib bet a, and GP IX), we tested the ability of the antibody to bind transfect ed cells that expressed different combinations of complex subunits, an d compared this binding to the binding of antibodies of known specific ity. SZ1 bound to cells that expressed the entire GP Ib-IX complex in the same pattern as did AN51 (an antibody specific for GP Ib alpha). H owever, unlike AN51, SZ1 did not bind alpha beta cells (ie, cells that express GP Ib alpha and GP Ib beta, but not GP IX), but did bind to b eta IX and alpha IX cells. We then compared the binding patterns of SZ 1 and FMC25, an antibody specific for GP IX. Both bound virtually iden tically to cell lines that expressed every combination of two of the t hree GP Ib-IX complex subunits. However, the epitopes of the two antib odies were not identical, because fixation with 4% paraformaldehyde of cells that expressed GP IX destroyed the SZ1 epitope while maintainin g the FMC25 epitope. Because of the ability of SZ1 to block the bindin g of many quinine- and quinidine-dependent antibodies, these data stro ngly suggest that GP IX is the component of the GP Ib-IX complex recog nized by those antibodies. (C) 1995 by The American Society of Hematol ogy.