Koponen M, Loor F
Ann Immunol (Paris). 1983 Sep-Oct;134D(2):207-22. doi: 10.1016/s0771-050x(83)80087-4.
Cyclosporin (Cs)-binding sites on murine spleen lymphocytes and on Cs-sensitive (CsS) and Cs-resistant (CsR) cloned lymphoma lines were compared using a ditritiated derivative of cyclosporin C (d3H-CsC). All three types of lymphocytes displayed similar d3H-CsC-binding characteristics. There were no major differences in the d3H-CsC-binding sites in terms of their cell surface density (number per surface area), their affinity and their specificity (capacity to discriminate between different Cs forms). The presence of the presumably membranous Cs-binding site is therefore insufficient to confer susceptibility to Cs, and resistance can thus be obtained at a post-receptor level. With the CsS clone, there was a general correlation between the Cs-specific binding capacity and the Cs-specific biological activity inasmuch as Cs which were weakly or not at all cytostatic bound only very poorly to the d3H-CsC-binding site. Such a correlation could not be established in the case of a mixed spleen cell population; which implies that, in such a system, Cs processing might play a role in its activity. Binding to the receptor may be an early but only a permissive step in the mechanism of action of Cs.
使用环孢菌素C的双氚化衍生物（d3H-CsC）比较了小鼠脾淋巴细胞以及环孢菌素敏感（CsS）和环孢菌素耐药（CsR）克隆淋巴瘤细胞系上的环孢菌素（Cs）结合位点。所有这三种类型的淋巴细胞均表现出相似的d3H-CsC结合特性。就其细胞表面密度（每表面积的数量）、亲和力和特异性（区分不同Cs形式的能力）而言，d3H-CsC结合位点没有重大差异。因此，推测的膜性Cs结合位点的存在不足以赋予对Cs的敏感性，因此可以在受体后水平获得耐药性。对于CsS克隆，Cs特异性结合能力与Cs特异性生物学活性之间存在普遍相关性，因为弱或完全没有细胞抑制作用的Cs与d3H-CsC结合位点的结合非常差。在混合脾细胞群体的情况下无法建立这种相关性；这意味着，在这样的系统中，Cs的加工过程可能在其活性中起作用。与受体结合可能是Cs作用机制中的早期但只是一个许可步骤。
