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Nat Immunol. 2009 Aug;10(8):831-9. doi: 10.1038/ni.1769. Epub 2009 Jul 13.

Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection.

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1
Nuffield Department of Clinical Medicine, Oxford University, UK.

Erratum in

  • Nat Immunol. 2010 Jan;11(1):97.

Abstract

T cell antigen receptor (TCR) signaling in CD4(+)CD8(+) double-positive thymocytes determines cell survival and lineage commitment, but the genetic and molecular basis of this process is poorly defined. To address this issue, we used ethylnitrosourea mutagenesis to identify a previously unknown T lineage-specific gene, Themis, which is critical for the completion of positive selection. Themis contains a tandem repeat of a unique globular domain (called 'CABIT' here) that includes a cysteine motif that defines a family of five uncharacterized vertebrate proteins with orthologs in most animal species. Themis-deficient thymocytes showed no substantial impairment in early TCR signaling but did show altered expression of genes involved in the cell cycle and survival before and during positive selection. Our data suggest a unique function for Themis in sustaining positive selection.

PMID:
19597497
PMCID:
PMC2908989
DOI:
10.1038/ni.1769
[Indexed for MEDLINE]
Free PMC Article

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