Themis controls thymocyte selection through regulation of T cell antigen receptor-mediated signaling.
Fu G., Vallée S., Rybakin V., McGuire MV., Ampudia J., Brockmeyer C., Salek M., Fallen PR., Hoerter JAH., Munshi A., Huang YH., Hu J., Fox HS., Sauer K., Acuto O., Gascoigne NRJ.
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.