High Density Lipoprotein-Specific Monoclonal Antibodies

Abstract

Mouse monoclonal antibodies that bind either human apolipoprotein (apo) AI or human apo AII were characterized with respect to their binding of high density lipoprotein (HDL) particles in solution. The single apo AII-specific antibody bound 85% of ¹²⁵I-HDL and 100% of soluble ¹²⁵I-apo AII. However, none of the three apo AI-specific antibodies bound greater than 60% of either HDL or soluble apo AI. Limiting amounts of antibody or antigen, radioiodination of the ligands, and unavailability of the epitopes for reaction with antibody were not responsible for the incomplete binding of HDL and apo AI, suggesting the existance of immunochemical heterogeneity of apo AI as organized on HDL as well as free apo AI in solution. The validity of this heterogeneity was supported by demonstrating that: i) increased binding of HDL occurred when each of the apo AI antibodies were combined to from an oligoclonal antibody mixture, and ii) 100% binding of HDL occurred when two apo AI antibodies were combined with the single apo AII antibody. These studies demonstrated that all apo AII peptides in plasma HDL possess at least one epitope in common, whereas the apo A I peptides in HDL are immunochemically heterogenous.