CYCLOSPORIN A AND ITS RECEPTOR (S)

Cyclosporin A (CsA) is a cyclic undecapeptide with selective immunosuppressive properties. It is widely used in humans to prevent allograft rejection of kidney, liver, heart, lung and bone marrow transplants. Most recently it has been found to inhibit the multiplication of HIV--1 (the causative agent of AIDS) A major objective of the ongoing research in this laboratory has been to clarify the basis of its unique immunosuppressive activity by identifying and eventually isolating cell receptors with which it interacts. Since CsA is also cytotoxic after prolonged administration it is of particular interest to distinguish interactions that lead to toxicity from those responsible for immunosuppression. This laboratory has recently identified a CsA receptor on the surface of lymphocytes that is associated with immunosuppression. This proposal describes the methods that we will use to isolate and characterize this receptor. The Specific Aims of this proposal are: 1. To isolate and purify the putative receptor and examine its interaction with CsA and with various lymphokines. 2. To obtain antibodies to the purified receptor and to test them for biologic activity. 3. To clone the receptor, exploiting the findings obtained in the pursuit of Specific Aims 2 and 3, and to compare its sequence with that of known receptors.