Characterization of Monoclonal Antibodies Against Human Low Density Lipoprotein

Characterization of Monoclonal Antibodies Against Human Low Density Lipoprotein
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抗人低密度脂蛋白单克隆抗体的表征

DOI:
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发表时间:
1983
期刊:
Arteriosclerosis
影响因子:
--
通讯作者:
Y. Marcel
Y. Marcel
中科院分区:
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文献类型:
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作者:
R. Milne;R. Theolis;R. Verdery;Y. Marcel

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已经对7种抗人低密度脂蛋白(LDL)的单克隆抗体就其特异性以及在培养的人成纤维细胞中干扰LDL途径的能力进行了鉴定。其中两种抗体(2D8和4G3)与LDL的免疫反应性对LDL中赖氨酸和精氨酸残基的修饰特别敏感。共滴定实验表明,抗体3A8和3A10可能与相同的决定簇发生反应,并且5种抗体(5E11、3A8、3A10、4G3和3F5)所识别的决定簇位于分子的同一区域。另外两种抗体(1D1和2D8)与远离该区域的决定簇发生反应。当以相对于LDL摩尔过量的方式进行测试时,5E11、3A8、3A10、4G3和3F5(但不是1D1或2D8)的Fab片段能够阻断125I - LDL与LDL受体的结合,并干扰培养的成纤维细胞中LDL对胆固醇合成的抑制作用。浓度增加10倍并没有显著改变结果。基于这些结果,我们提出了一个LDL中决定簇的图谱。
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 flbroblasts. The Immunoreactivity with LDL of two of the antibodies (2D8 and 4G3) was particularly sensitive to modification of lysine and arginlne 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 125 I-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.
DOI: 10.1126/science.6261329
发表时间: 1981-01-01
期刊: SCIENCE
影响因子: 56.9
作者:
BROWN, MS;KOVANEN, PT;GOLDSTEIN, JL
通讯作者: GOLDSTEIN, JL