Aston R, Holder A T, Ivanyi J, Bomford R
Mol Immunol. 1987 Feb;24(2):143-50. doi: 10.1016/0161-5890(87)90086-1.
Monoclonal antibodies (MAbs) prepared against ovine growth hormone (oGH) and recognizing several distinct or related specificities on bovine growth hormone (bGH), have been shown to strikingly enhance the growth promoting properties of the hormone in vivo as determined by 35SO2-4 incorporation in cartilage. The phenomenon is dependent on both hormone and antibody dose and is saturable in the presence of excess antibody. Competition binding analysis between pairs of antibodies has shown that they define distinct antigenic regions on bGH of which one is represented by four MAbs. The most potent growth enhancement was associated with a group of three MAbs (OA11, OA12 and OA13) binding to topographically closely related sites. Another MAb (OA14) with a specificity similar to OA11 and OA13 as defined by competition assay failed to enhance bGH activity. Two antibodies binding to a further two sites (OA15 and OA16) demonstrated modest growth enhancement activity when in complex with bGH, whereas the binding of another antibody (OA17) did not significantly affect hormonal activity. Univalent antibody fragments (Fab) derived from MAb OA11 were equi-potent to the bivalent form of the antibody in the enhancement of bGH activity. Determination of the effects of the different MAbs on the binding of 125I-bGH to liver microsome receptors revealed substantial increase in specific binding (3.5-fold) and is associated with some growth enhancing MAbs. However, not all growth enhancing MAbs increased receptor binding and in the case of one, OA16, clear cut inhibition of receptor binding was observed. Tentative conclusions have been drawn on the possible underlying mechanisms of the MAb mediated enhancement phenomenon.
针对绵羊生长激素（oGH）制备的单克隆抗体（MAb），能够识别牛生长激素（bGH）上几种不同或相关的特异性，已证明这些抗体可显著增强该激素在体内的促生长特性，这一特性通过软骨中35SO2-4的掺入量来确定。该现象取决于激素和抗体的剂量，并且在存在过量抗体的情况下是可饱和的。对成对抗体之间的竞争结合分析表明，它们定义了bGH上不同的抗原区域，其中一个区域由四种单克隆抗体代表。最强的生长增强作用与一组结合在拓扑结构紧密相关位点的三种单克隆抗体（OA11、OA12和OA13）有关。通过竞争试验确定，另一种与OA11和OA13特异性相似的单克隆抗体（OA14）未能增强bGH活性。与bGH结合时，另外两种结合到另外两个位点的抗体（OA15和OA16）表现出适度的生长增强活性，而另一种抗体（OA17）的结合并未显著影响激素活性。源自单克隆抗体OA11的单价抗体片段（Fab）在增强bGH活性方面与抗体的二价形式等效。测定不同单克隆抗体对125I-bGH与肝微粒体受体结合的影响，结果显示特异性结合显著增加（3.5倍），并且与一些具有生长增强作用的单克隆抗体有关。然而，并非所有具有生长增强作用的单克隆抗体都会增加受体结合，对于其中一种抗体OA16，观察到明显的受体结合抑制。已就单克隆抗体介导的增强现象的可能潜在机制得出初步结论。
