THE CAMPATH-1 ANTIGEN CDW52
THE CAMPATH-1 ANTIGEN CDW52
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DOI：
10.1111/j.1399-0039.1990.tb01767.x
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发表时间：
1990-01-01
期刊：
影响因子：
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通讯作者：
WALDMANN H
中科院分区：
文献类型：
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作者：
HALE G;XIA M-Q;WALDMANN H
所有证据表明，CDw52抗体识别碳水化合物表位，可能是o -连接的低聚糖。在人类中，表位似乎主要或完全表达在一个特定的淋巴细胞糖蛋白上，其表观分子量为21- 28kd。我们预计使用表达系统分离同源cDNA将会很困难；事实上，尝试使用一种流行的方法来做到这一点是不成功的（H. Waldmann和D. Simmonds，未发表的数据）。从组织切片的免疫过氧化物酶染色和YTH 361.10的有丝分裂活性可以看出，一些运动腺肽-1抗体（IgM和IgG2c）可能与其他分子发生弱交叉反应。在猴子中，抗原表位也可以在红细胞中表达，可能以糖脂的形式表达。它在几乎所有分化阶段的淋巴细胞上广泛表达，使其成为淋巴样肿瘤免疫治疗的有用靶抗原。尽管所有的结构研究，我们还没有充分解释其不寻常的能力赋予敏感性补体介导的裂解。相对较高的抗原密度(约5。105个分子/细胞)和缺乏调节必须是重要的因素，但单独似乎是不够的，因为其他抗原是裂解的不良靶标（如CD45）具有类似的性质（25）。也许在每个抗原分子上有多个相同的表位，因此多个抗体可以同时结合，导致“协同”裂解（36）。多个糖基化位点的模式可能解释了Western blotting上看到的“阶梯”带（图2）。然而，这并不符合cpath - 1m无法引起补片或封顶的情况。campaign -1抗原在有机溶剂中的不寻常溶解度表明它不是一种传统的膜糖蛋白。我们相信，更详细的结构研究将产生回报，正如抗体本身将找到有用的临床应用。
All the evidence suggests that the CDw52 antibodies recognise a carbohydrate epitope, probably an O-linked oligosaccharide. In humans the epitope seems to be mainly or exclusively expressed on a specific lymphocyte glycoprotein with an apparent molecular weight of 21-28 kD. We anticipate that it will be difficult to isolate the cognate cDNA using expression systems; indeed, attempts to do so using a popular method were unsuccessful (H. Waldmann and D. Simmonds, unpublished data). Some of the CAMPATH-1 antibodies (IgM and IgG2c) may cross-react weakly with other molecules, as suggested by the immunoperoxidase staining of tissue section and the mitogenic activity of YTH 361.10. In monkeys the antigenic epitope can also be expressed in red cells, possibly as a glycolipid. Its wide expression on lymphocytes at nearly all stages of differentiation makes it a useful target antigen for attempts at immunotherapy of lymphoid neoplasia. Despite all of the structural studies, we have not adequately explained its unusual ability to confer sensitivity to complement mediated lysis. The relatively high density of antigen (approx 5 .times. 105 molecules/cell) and lack of modulation must be important factors, but alone seem insufficient since other antigens which are poor targets for lysis (eg CD45) have similar properties (25). Perhaps there are multiple identical epitopes on each antigen molecule so that more than one antibody can bind simultaneously, leading to 'synergistic' lysis (36). A pattern of multiple glycosylation sites might account for the 'ladder' of bands seen on Western blotting (Fig. 2). However, this does not fit in with the inability of CMPATH-1M to cause patching or capping. The unusual solubility of the CAMPATH-1 antigen in organic solvents suggests that it is not quite a conventional membrane glycoprotein. We are convinced that more detailed structural studies will yield rewards, just as the antibodies themselves will find useful clinical applications.