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Themis (thymocyte-expressed molecule involved in selection), a member of a family of proteins with unknown functions, is highly conserved among vertebrates. Here we found that Themis had high expression in thymocytes between the pre-T cell antigen receptor (pre-TCR) and positive-selection checkpoints and low expression in mature T cells. Themis-deficient thymocytes showed defective positive selection, which resulted in fewer mature thymocytes. Negative selection was also impaired in Themis-deficient mice. A greater percentage of Themis-deficient T cells had CD4(+)CD25(+)Foxp3(+) regulatory and CD62L(lo)CD44(hi) memory phenotypes than did wild-type T cells. In support of the idea that Themis is involved in TCR signaling, this protein was phosphorylated quickly after TCR stimulation and was needed for optimal TCR-driven calcium mobilization and activation of the kinase Erk.

Original publication

DOI

10.1038/ni.1766

Type

Journal article

Journal

Nat Immunol

Publication Date

08/2009

Volume

10

Pages

848 - 856

Keywords

Amino Acid Sequence, Animals, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Lineage, Cell Survival, Cells, Cultured, Cloning, Molecular, Female, Flow Cytometry, Humans, Mice, Mice, Knockout, Molecular Sequence Data, Oligonucleotide Array Sequence Analysis, Organ Specificity, Proteins, Receptors, Antigen, T-Cell, Signal Transduction