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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.

Original publication

DOI

10.1038/ni.1769

Type

Journal article

Journal

Nat immunol

Publication Date

08/2009

Volume

10

Pages

831 - 839

Keywords

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