The definitive maker of the T lineage is rearrangement and expression of T cell receptor(TCR). The first step is TCR beta-chain rearrangement from the individual V, D and J elements. This rearrangement is preceded by transcription of the locus in the germline configuration from a progenitor T cell specific promoter upstream of the TCR Dbeta1 element. My hypothesis is that the TCR Dbeta1 germline promoter is regulated by progenitor T restricted transcription factors which play a key role in linage development.
My aims are to identify both cis element and trans-acting DNA binding factors which regulate TCR beta germline transcription and to characterize the regulation of these transcripts in early T cell precursors in vivo. Identification of progenitor T cell specific transcription factors will allow us to determine their role in T linage development. Identifying which cells express the TCR D region transcription may provide insight into how a common lymphoid precursor develops into either a T cell or a B cell. Understanding the process leading to antigen rearrangement will provide fundamental insight into the regulation of rearrangement leading to both normal and neoplastic development. Furthermore, understanding the regulatory steps leading to linage development should provide the ability to increase normal lymphopoiesis in individuals suffering from depressed lymphocyte count induced by diseases such as AIDS, or treatment regimens such as chemotherapy
