title: Anti-apoprotein B monoclonal antibodies detect human low density lipoprotein polymorphism.
abstract: Immunochemical polymorphism among human low density lipoproteins (LDL) isolated from different individuals was demonstrated through reduced binding of three monoclonal antibodies to some individual LDL using a solid phase radioimmunoassay. These three antibodies are members of a larger group of monoclonal antibodies previously shown to bind specifically to apoprotein B ( Curtiss , L.K., and Edgington , T. S. (1982) J. Biol. Chem. 257, 15213-15221; Tsao , B.P., Curtiss , L. K., and Edgington , T.S. (1982) J. Biol. Chem. 257, 15222-15228). Those antibodies which distinguished human LDL polymorphism bound to the same or adjacent epitopes on LDL, for they were mutually exclusive in competitive binding experiments. Binding was unaffected by treatment with neuraminidase, with a mixture of glycosidases, or with competing glycoproteins; thus, the carbohydrate moiety of apoprotein B did not appear to influence the epitope recognized by these antibodies. When low density lipoproteins isolated from different individuals were studied, three different phenotypes were recognized; these corresponded to strong, weak, and intermediate binding of the three monoclonal antibodies. This division into three phenotypes is demonstrated to result from a genetic polymorphism; indeed, the data fit a model consisting of two co-dominant apoprotein B alleles, and the three phenotypes then correspond to the two human homozygotes and the heterozygote. The classical Ag antigen phenotype was determined for the LDL isolated from 10 individuals who were also studied with the monoclonal antibodies, and no correspondence was found between the different epitopes recognized by the five presumptive Ag allelic pairs, x/y, a1/d, c/g, t/z, or h/i, and the site recognized by the monoclonal antibodies. All of these data are discussed, and it is concluded that the most likely explanation for the difference in recognition of the two allelic forms of apoprotein B is an alteration in amino acid sequence resulting in a slightly different configuration of a single domain containing the epitopes recognized by the three monoclonal antibodies.
mesh_terms: D000911:Antibodies, Monoclonal; D001053:Apolipoproteins / Q000097:blood* / Q000235:genetics; D001055:Apolipoproteins B; D001667:Binding, Competitive; D002241:Carbohydrates / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D011863:Radioimmunoassay
chemical_list: D000911:Antibodies, Monoclonal; D001053:Apolipoproteins; D001055:Apolipoproteins B; D002241:Carbohydrates