During positive selection, thymocytes transition through a stage during which T cell antigen receptor (TCR) signaling controls CD4-versus-CD8 lineage selection and maturation. Thymocyte-expressed molecule involved in selection (themis) is critically required for this thymocyte selection. Themis has been identified as several molecules: Grb2-associating protein (GASP), signaling phosphoprotein specific for T cells (SPoT), TSEPA, and thylex. Themis is a cytosolic protein with no known functional motifs. Its expression is observed primarily in T cells, especially immature CD4/CD8 double positive thymocytes. Themis-deficient thymocytes have defective positive selection, and fewer numbers of mature thymocytes. These themis-induced effects may be due to defective TCR signaling since themis constitutively associates with the TCR adaptor Grb2, and themis is phosphorylated quickly after TCR stimulation. In addition, themis is required for optimal TCR-driven calcium mobilization and activation of the MAP kinase Erk. Thus, themis may be an important adaptor protein in TCR signaling.
