Cyclosporin-binding sites of murine sensitive and resistant lymphoid cell lines

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.