Study of immunosuppressive activity of a synthetic decapeptide corresponding to an ACTH-like sequence of human immunoglobulin G1

The synthetic ACTH-like decapeptide H-Val-Lys-Lys-Pro-Gly-Ser-Ser-Val-Lys-V al-OH, corresponding to amino acid residues 11-20 of the variable part of t he human IgG1 heavy chain (referred to as immunocortin) was found to have a n immunosuppressive effect On cells in vitro: it inhibits blast transformat ion of mouse thymocytes and reduces spontaneous motility of mouse peritonea l macrophages as well as their bactericidal activity against the virulent b acterial strain Salmonella typhimurium 415. Tritium-labeled immunocortin bi nds with high affinity to ACTH receptors on thymocytes and macrophages (K-d 2.1 and 2.5 nM, respectively) and activates adenylate cyclase in these cel ls. Thus, the interaction of immunocortin with the target cell includes the following main steps: binding to the receptor, activation of adenylate cyc lase, and elevation of the intracellular content of cAMP.