T cell development requires the migration of haematopoietic progenitors from the bone marrow to the thymus. T cell lineage potential is broadly distributed among primitive bone marrow-derived progenitor populations. However, the ability to migrate to the thymus is tightly regulated. Thymic homing has a molecular basis that is beginning to be understood. Known molecules implicated in thymic homing include P-selectin glycoprotein ligand 1 and the chemokine receptors CCR7 and CCR9. Migration of developing thymocytes through different regions of the thymus is crucial for normal T cell development and is regulated by multiple chemokine receptors, including CXCR4, CCR7 and CCR9. Crosstalk between these receptors and developmental receptors (the T cell receptor (TCR) and pre-TCR) regulates both thymocyte migration and thymocyte development. Thymocyte emigration is precisely timed to occur only after maturation is completed and after thymocytes are screened by negative selection to remove overtly autoreactive cells. The chemotactic receptor sphingosine-1-phosphate receptor 1 (S1P₁; encoded by S1PR1) has a crucial role in regulating thymocyte export. Current data suggest a model for thymocyte emigration in which TCR signalling controls the timing of export by regulating the expression of S1P₁ and CCR7, as well as that of CD69, which functions to downregulate S1P₁ surface expression. TCR signals inhibit S1pr1 transcription and upregulate CD69, thereby preventing thymocyte export. Cessation of TCR signalling induces S1pr1 transcription and downregulates CD69, rendering thymocytes susceptible to S1P₁-mediated signalling and promoting thymocyte emigration.

Signal transduction by the T-cell antigen receptor (TCR) is initiated by phosphorylation of conserved motifs (ITAMs) contained within the cytoplasmic domains of the invariant subunits. TCR complexes contain a total of 10 ITAMs and this unusual configuration has prompted studies of the role of specific ITAMs, or of ITAM multiplicity, in regulating TCR-directed developmental and effector responses. Here, we summarize data generated during the past two decades and discuss how these findings have in some cases resolved, and in others complicated, outstanding questions relating to the function of TCR ITAMs.