title: Inhibition of human natural killer cell activity by a synthetic peptide homologous to a conserved region in the retroviral protein, p15E.
abstract: It has been shown previously that the retroviral envelope protein p15E suppresses certain monocyte and lymphocyte functions. In this paper, we describe the effects on natural killer (NK) activity of a synthetic peptide (CKS-17) with homology to a region of p15E conserved among numerous retroviruses. Enriched human NK cells were assayed against K562 tumor target cells in a 51Cr-release cytotoxicity assay. Pretreatment of NK cells with CKS-17 at concentrations as low as 1.5 microM, but not with equivalent concentrations of control materials, markedly and reproducibly suppressed NK lytic activity. Prior exposure of NK cells to interferon-alpha (IFN-alpha) at 1000 U/ml did not alter their sensitivity to CKS-17-induced inhibition. Pretreating NK cells with CKS-17 almost entirely diminished their responsiveness to IFN-alpha and IFN-gamma, but not to interleukin 2 (IL 2). Kinetics experiments demonstrated that CKS-17-mediated suppression of both endogenous and activated NK cells was reversible after 18 hr at 37 degrees C. Experiments designed to examine the CKS-17 mechanism of action revealed that the peptide bound to all Leu-11+ lymphocytes, as shown by two-color flow cytometry. CKS-17 did not, however, inhibit effector cell/target cell conjugate formation. These data suggest a new mechanism for immune suppression mediated by retroviruses; inhibition of NK function. They moreover imply that the CKS-17 peptide interferes with the lytic phase of NK cytolysis.
mesh_terms: D000293:Adolescent; D000328:Adult; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015683:Gene Products, gag; D006801:Humans; D007108:Immune Tolerance; D007372:Interferons / Q000494:pharmacology; D007376:Interleukin-2; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D007700:Kinetics; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D012190:Retroviridae; D012191:Retroviridae Proteins / Q000494:pharmacology*; D015682:Retroviridae Proteins, Oncogenic; D012710:Serum Albumin, Bovine / Q000494:pharmacology
chemical_list: D015683:Gene Products, gag; D007376:Interleukin-2; D010455:Peptides; D012191:Retroviridae Proteins; D015682:Retroviridae Proteins, Oncogenic; C039467:virus structural protein p15; D012710:Serum Albumin, Bovine; D007372:Interferons