Vogel M, Miescher S, Kuhn S, Zürcher A W, Stadler M B, Ruf C, Effenberger F, Kricek F, Stadler B M
Institute of Immunology and Allergology, Sahli Haus 2, Inselspital, 3010, Switzerland.
J Mol Biol. 2000 May 19;298(5):729-35. doi: 10.1006/jmbi.2000.3713.
According to Jerne's network hypothesis, the binding site of an anti-idiotypic antibody also represents the internal image of an epitope present on a foreign, or even a self antigen. In recent years, antigen mimicry has been defined at the molecular level for some xeno-antigens. However, until now there has been no demonstration of structural mimicry between a human anti-idiotypic antibody and a self structure. To address this question, we used human IgE as the self structure and a well-defined anti-human IgE mAb (BSW17). We describe the isolation of two anti- idiotypic antibodies specific for the anti-IgE antibody BSW17 from a non-immune human Fab phage display library. Interestingly, these two anti-idiotypic antibodies mimic the same molecular surface region as a previously described IgE peptide mimotope isolated by panning on BSW17, but they cover a much larger epitope on the IgE molecule. Accordingly, immunisation of rabbits with the two anti-idiotypic antibodies induced high-affinity antibodies with the same characteristics as BSW17. Thus, our data demonstrate that it is possible to isolate anti-idiotypic antibodies derived from the human genome without the need for hyperimmunization, and confirm Jerne's hypothesis that both foreign antigens and self structures can be mimicked by our own immunoglobulins.
根据耶尔恩的网络假说，抗独特型抗体的结合位点也代表了存在于外来甚至自身抗原上的表位的内影像。近年来，已经在分子水平上对一些异种抗原的抗原模拟进行了定义。然而，到目前为止，尚未证明人抗独特型抗体与自身结构之间存在结构模拟。为了解决这个问题，我们将人IgE用作自身结构，并使用了一种明确的抗人IgE单克隆抗体（BSW17）。我们描述了从非免疫人Fab噬菌体展示文库中分离出两种对抗IgE抗体BSW17具有特异性的抗独特型抗体。有趣的是，这两种抗独特型抗体模拟了与先前通过淘选BSW17分离出的IgE肽模拟表位相同的分子表面区域，但它们覆盖了IgE分子上更大的表位。因此，用这两种抗独特型抗体免疫兔子可诱导出具有与BSW17相同特性的高亲和力抗体。因此，我们的数据表明，无需超免疫就有可能从人类基因组中分离出抗独特型抗体，并证实了耶尔恩的假说，即外来抗原和自身结构都可以被我们自身的免疫球蛋白模拟。
