Characterization of monoclonal antibodies against human low density lipoprotein.
Seven monoclonal antibodies against human low density lipoprotein (LDL) have been characterized as to their specificity and ability to interfere with the LDL pathway in cultured human fibroblasts. The immunoreactivity with LDL of two of the antibodies (2D8 and 4G3) was particularly sensitive to modification of lysine and arginine residues in LDL. Cotitration experiments indicated that the antibodies 3A8 and 3A10 may react with the same determinant and that five antibodies (5E11, 3A8, 3A10, 4G3 and 3F5) recognized determinants that were grouped in the same region of the molecule. The two other antibodies (1D1 and 2D8) reacted with determinants distant from this region. When tested in molar excess relative to LDL, Fab fragments of 5E11, 3A8, 3A10, 4G3 and 3F5 (but not 1D1 or 2D8) were capable of blocking the binding of 125I-LDL to the LDL receptor and interfering with LDL suppression of cholesterol synthesis in cultured fibroblasts. Increasing the concentration 10-fold did not change the results significantly. Based on these results we have proposed a map of the determinants as they would appear in LDL.
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001053:Apolipoproteins / Q000032:analysis; D001055:Apolipoproteins B; D003429:Cross Reactions; D000939:Epitopes / Q000032:analysis; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology*; D011863:Radioimmunoassay
D000911:Antibodies, Monoclonal; D001053:Apolipoproteins; D001055:Apolipoproteins B; D000939:Epitopes; D008077:Lipoproteins, LDL