Signaling microdomains in T cell development
This project is aimed at characterizing the molecular mechanisms regulating an early phase of T lymphocyte development, namely expansion and differentiation driven by the pre-T cell receptor (pre-TCR) in the thymus. The characterization of molecular mechanisms involved in pre-TCR signaling will elucidate the regulation of lymphocyte growth and differentiation at this early checkpoint in T cell development. This could have general implications in the understanding of signaling by transmembrane receptors. The pre-TCR shares several features of oncogenic receptors and could be oncogenic in particular genetic contexts, then the proposed experiments could likewise reveal important mechanisms in the control of growth and differentiation of eukaryotic cells whose failure could result in leukemia as well as other cancers. Another relevant issue addressed by this project is the immune reconstitution in pathologic conditions such as AIDS or following cytoablative therapeutic regimens. Here the characterization of the events controlling early T cell expansion could suggest therapeutic strategies to implement immune reconstitution, thus decreasing infectious complications and malignant relapses.