BIOLOGICAL SIGNIFICANCE OF CARBOHYDRATE CHAINS ON MONOCLONAL-ANTIBODIES

BIOLOGICAL SIGNIFICANCE OF CARBOHYDRATE CHAINS ON MONOCLONAL-ANTIBODIES
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DOI:
10.1073/pnas.80.21.6632
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发表时间:
1983-01-01
期刊:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子:
--
通讯作者:
WIGZELL, H
WIGZELL, H
中科院分区:
其他
文献类型:
--
作者:
NOSE, M;WIGZELL, H

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用tunicamycin处理杂交瘤细胞,制备了去除天冬酰胺碳水化合物链的半抗原特异性小鼠IgG2b单克隆抗体。在优良的抗原结合反应性(Fab片段特征)和蛋白a结合能力(H链恒定区CH2和CH3结构域相互作用区域的完整性特征)方面,缺乏碳水化合物的抗体与正常抗体表现相同。它们失去了激活补体、与巨噬细胞上的Fc受体结合以及诱导抗体依赖性细胞毒性的能力。由这种缺乏碳水化合物的抗体产生的抗原-抗体复合物不能迅速从循环中消除。从IgG分子中去除碳水化合物链可能会对这些抗体的生物活性产生深远而高度选择性的影响。
Monoclonal hapten-specific mouse IgG2b antibodies depleted of asparagine-linked carbohydrate chains were prepared by treating the hybridoma cells with tunicamycin. The carbohydrate-deficient antibodies behaved in an identical manner to the normal antibodies with regard to fine antigen-binding reactivity (a Fab fragment feature) and protein A binding capacity [a feature requiring integrity at the CH2 and CH3 domain-interation regions in the constant region of the H chain (CH)]. They lost the ability to activate complement, to bind to Fc receptors on macrophages, and to induce antibody-dependent cellular cytotoxicity. Antigen-antibody complexes produced from such carbohydrate-deficient antibodies failed to be eliminated rapidly from the circulation. Removal of carbohydrate chains from IgG molecules may have a profound and highly select impact on the biological activity to these antibodies.