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Peptide-induced negative selection of thymocytes activates transcription of an NF-kappa B inhibitor

Fiorini, Emma and Reche, Pedro A Peptide-induced negative selection of thymocytes activates transcription of an NF-kappa B inhibitor.

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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.


Item Type:Article
Subjects:Medical sciences > Medicine > Immunology
Medical sciences > Biology > Molecular biology
ID Code:9342
Deposited On:17 Aug 2009 08:49
Last Modified:17 Nov 2011 09:21

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