Peptide-induced Negative Selection of Thymocytes Activates Transcription of an NF-kappa B Inhibitor

Mol Cell. 2002 Mar;9(3):637-48. doi: 10.1016/s1097-2765(02)00469-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Fractionation
  • Cell Separation
  • Flow Cytometry
  • Genes, Reporter
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Peptides / metabolism*
  • Proteins / chemistry
  • Proteins / genetics*
  • Proteins / metabolism*
  • Receptors, Antigen, T-Cell / physiology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • T-Lymphocytes / physiology*
  • Thymus Gland / cytology
  • Transcription, Genetic*
  • Transduction, Genetic

Substances

  • IkappaBNS protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • Peptides
  • Proteins
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins

Associated data

  • GENBANK/AY078069