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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Fiorini E,Schmitz I,Marissen WE,Osborn SL,Touma M,Sasada T,Reche PA,Tibaldi EV,Hussey RE,Kruisbeek AM,Reinherz EL,Clayton LK

doi

10.1016/s1097-2765(02)00469-0

subject

Has Abstract

pub_date

2002-03-01 00:00:00

pages

637-48

issue

3

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(02)00469-0

journal_volume

9

pub_type

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