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Abstract

The molecular basis for T cell receptor signaling events that lead to differential cellular immune responses has been a fundamental question in immunology. For example, the molecular mechanism governing positive and negative T cell selection during thymocyte development has remained elusive. Furthermore, the mechanisms governing variable T cell receptor-mediated responses of different T cell subsets, such as memory and naive T cells have remained unclear. In a gain-of-function transgenic strategy, we have established that augmented CD45R⁰ expression enhanced the efficacy of TCR signaling and TCR-mediated apoptosis of immature CD4⁺CD8⁺ thymocytes in vitro. Furthermore, CD45 was also found to regulate both positive and negative selection events during thymocyte development. In addition, CD45 was determined to be a marker for a population of thymocytes undergoing positive selection. We have further demonstrated that distinct CD45 isoforms have differential functions in T cell activation and signaling in mature thymic T cells as well as differentially regulating thymocyte development.