title: Peptide-induced negative selection of thymocytes activates transcription of an NF-kappa B inhibitor.
abstract: Negative selection eliminates thymocytes bearing autoreactive T cell receptors (TCR) via an apoptotic mechanism. We have cloned an inhibitor of NF-kappa B, I kappa BNS, which is rapidly expressed upon TCR-triggered but not dexamethasone- or gamma irradiation-stimulated thymocyte death. The predicted protein contains seven ankyrin repeats and is homologous to I kappa B family members. In class I and class II MHC-restricted TCR transgenic mice, transcription of I kappa BNS is stimulated by peptides that trigger negative selection but not by those inducing positive selection (i.e., survival) or nonselecting peptides. I kappa BNS blocks transcription from NF-kappa B reporters, alters NF-kappa B electrophoretic mobility shifts, and interacts with NF-kappa B proteins in thymic nuclear lysates following TCR stimulation. Retroviral transduction of I kappa BNS in fetal thymic organ culture enhances TCR-triggered cell death consistent with its function in selection.
authors.affiliation: Laboratory of Immunobiology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Fiorini
authors.forename: Ingo
authors.initials: I
authors.lastname: Schmitz
authors.forename: Wilfred E
authors.initials: WE
authors.lastname: Marissen
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Osborn
authors.forename: Maki
authors.initials: M
authors.lastname: Touma
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sasada
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Reche
authors.forename: Elena V
authors.initials: EV
authors.lastname: Tibaldi
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Hussey
authors.forename: Ada M
authors.initials: AM
authors.lastname: Kruisbeek
authors.forename: Ellis L
authors.initials: EL
authors.lastname: Reinherz
authors.forename: Linda K
authors.initials: LK
authors.lastname: Clayton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002458:Cell Fractionation; D002469:Cell Separation; D005434:Flow Cytometry; D017930:Genes, Reporter; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology; D014158:Transcription, Genetic; D014161:Transduction, Genetic
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D010455:Peptides; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; C454819:Nfkbid protein, mouse