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

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.

Pubmed ID: 19597497

Authors

  • Johnson AL
  • Aravind L
  • Shulzhenko N
  • Morgun A
  • Choi SY
  • Crockford TL
  • Lambe T
  • Domaschenz H
  • Kucharska EM
  • Zheng L
  • Vinuesa CG
  • Lenardo MJ
  • Goodnow CC
  • Cornall RJ
  • Schwartz RH

Journal

Nature immunology

Publication Data

August 21, 2009

Associated Grants

  • Agency: Medical Research Council, Id: G0700830
  • Agency: Intramural NIH HHS, Id: Z01 AI000485-21
  • Agency: Medical Research Council, Id:
  • Agency: Wellcome Trust, Id:

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cell Differentiation
  • Cell Line
  • Cell Lineage
  • Cell Survival
  • Ethylnitrosourea
  • Female
  • Humans
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Proteins
  • Receptors, Antigen, T-Cell
  • Signal Transduction