title: Suppression of lymphocyte proliferation by a retroviral p15E-derived hexapeptide.
abstract: CKS-17 (LQNRRGLDLLFLKEGGL), a synthetic peptide derived from a conserved region of retroviral transmembrane proteins, has previously been shown to suppress several different immune effector mechanisms. The present study was undertaken to further delineate immunosuppressive site(s) of CKS-17. Overlapping hexapeptides covering the complete sequence of CKS-17 were synthesized. One CKS-17-derived hexapeptide, LDLLFL, suppressed ligand [CD3, interleukin (IL)-2]-induced lymphocyte proliferation. Spontaneous proliferation of transformed lymphoid cell lines, as well as cell lines from myeloid or epitheloid origin, was not inhibited by LDLLFL. Full suppression required the continuous presence of LDLLFL during culturing, and did not involve interference with monocyte function. Radiolabeling studies showed that the hexapeptide did not compete with IL-2 for IL-2 receptor binding. Most likely the LDLLFL motif interferes with steps shared by the IL-2 and CD3 receptor-induced signaling pathways. Since LDLLFL displays multiple immunosuppressive activities, it may constitute a biologically relevant immunosuppressive site of retroviral transmembrane proteins.
authors.affiliation: Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: R A
authors.initials: RA
authors.lastname: Oostendorp
authors.forename: W M
authors.initials: WM
authors.lastname: Schaaper
authors.forename: J
authors.initials: J
authors.lastname: Post
authors.forename: B M
authors.initials: BM
authors.lastname: Von Blomberg
authors.forename: R H
authors.initials: RH
authors.lastname: Meloen
authors.forename: R J
authors.initials: RJ
authors.lastname: Scheper
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D017252:CD3 Complex; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects*; D036341:Intercellular Signaling Peptides and Proteins; D007376:Interleukin-2 / Q000494:pharmacology; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000276:immunology*; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D036341:Intercellular Signaling Peptides and Proteins; D007376:Interleukin-2; D010446:Peptide Fragments; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; C053692:CKS 17