Mapping of human apolipoprotein B antigenic determinants.
A minimum of 16 epitopes which provide a group of topographical markers to study the conformation of apolipoprotein (apo) B have been mapped in relation to elements of the sequence of apo B-100. Six of these epitopes are identified by monoclonal antibodies (Mabs) directed against low density lipoprotein (LDL) apo B, while at least 10 others react with Mabs obtained by immunization with delipidated and solubilized apo B. Five epitopes which are also expressed on apo B-48 have been assigned to the thrombolytic fragment T4 on the N-terminal side of apo B-100. None of these five epitopes requires the presence of lipids for its expression, suggesting that the conformation of the T4 region of apo B is more dependent on peptide-chain interactions than on peptide-lipid interactions. Four distinct epitopes have been assigned to the median thrombolytic fragment T3 of apo B-100, all of which require the presence of lipids for their expression; those epitopes closer to the C-terminus of T3 require specific interaction with cholesteryl esters. The same lipid dependence also characterizes a cluster of epitopes mapped to the N-terminal region of fragment T2. The epitopes that are close to the T2/T3 cleavage site and depend on the presence of cholesteryl esters for their expression are also those that react with the Mabs that inhibit the binding of LDL to its receptor. Therefore this region, which in addition contains two sequences with structural homology to the apo E receptor binding domain, probably constitutes a physiologically important receptor binding site for apo B. Finally, four other distinct epitopes which do not require the presence of lipids for their expression have been mapped on T2. In conclusion, the present report presents evidence that the immunochemical analogy of apo B-48 and apo B-100 is on the N-terminal half of apo B-100, whereas the apo B receptor binding domain is localized on the C-terminal half of apo B-100 close to the T2/T3 cleavage site.
D000911:Antibodies, Monoclonal / Q000276:immunology; D001055:Apolipoproteins B / Q000276:immunology*; D001665:Binding Sites; D000939:Epitopes; D006801:Humans; D007163:Immunosorbent Techniques; D008077:Lipoproteins, LDL / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D011973:Receptors, LDL / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001055:Apolipoproteins B; D000939:Epitopes; D008077:Lipoproteins, LDL; D010446:Peptide Fragments; D011973:Receptors, LDL; D013917:Thrombin