IMMUNOREACTIVITY OF APO-B TOWARDS MONOCLONAL-ANTIBODIES THAT INHIBIT THE LDL-RECEPTOR INTERACTION - EFFECTS OF LDL OXIDATION

We studied the immunochemical stability of the epitopes for six monocl onal antibodies to human apolipoprotein B-100 upon Cu2+-mediated (20 m uM) oxidation of LDL. The antibodies used in this study, some of which are known to interfere with the interaction of LDL with their cellula r receptors, recognize epitopes in the amino terminal region (Mb 19), in the middle part (6B, 2A, 7A, and 9A) and near aa 3500 (Mb 47) of na tive apo B. All antibodies except one (7A) recognized native and oxidi zed LDL (OxLDL) equally well; the immunoreactivity of the epitope for Ab 7A was markedly reduced upon LDL oxidation. Since antibodies 2A, 7A , 9A, and Mb 47 inhibit the LDL-receptor interaction and OxLDL poorly interact in vitro with the LDL receptor we conclude that: (1) various epitopes for monoclonal antibodies against native apo B are spared upo n LDL oxidation; and (2) the epitopes for antibodies 2A, 9A, and Mb 47 do not define a unique domain of apo B directly involved in the bindi ng of LDL to their receptor.