2Institute of Engineering Immunology, Lyubuchany, Moscow Region, 142380 Russia; fax: (095) 546-1574
* To whom correspondence should be addressed.
Received February 11, 1999
The synthetic ACTH-like decapeptide H-Val-Lys-Lys-Pro-Gly- Ser-Ser-Val-Lys-Val-OH, corresponding to amino acid residues 11-20 of the variable part of the human IgG1 heavy chain (referred to as immunocortin) was found to have an immunosuppressive effect on cells in vitro: it inhibits blast transformation of mouse thymocytes and reduces spontaneous motility of mouse peritoneal macrophages as well as their bactericidal activity against the virulent bacterial strain Salmonella typhimurium 415. Tritium-labeled immunocortin binds with high affinity to ACTH receptors on thymocytes and macrophages (Kd 2.1 and 2.5 nM, respectively) and activates adenylate cyclase in these cells. Thus, the interaction of immunocortin with the target cell includes the following main steps: binding to the receptor, activation of adenylate cyclase, and elevation of the intracellular content of cAMP.
KEY WORDS: adrenocorticotropic hormone (ACTH), immunoglobulin G (IgG), peptides, receptors, adenylate cyclase, thymocytes, peritoneal macrophages, immune system