Role of Shcbp1 (mPAL) in T Cell Development and Function

University Of Virginia, Charlottesville VA

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Abstract

DESCRIPTION (provided by applicant): T cell development in the thymus and T cell activation are highly regulated processes, and dysregulation of genes and pathways involved in normal T cell development and activation can lead to the emergence of T cell leukemias and lymphomas. The molecular mechanisms that control normal T cell development are also involved in oncogenetic transformation, and understanding normal development may lead to new therapeutic targets for T cell leukemia and lymphoma. Our studies focus on the role of a novel protein, Shcbp1, in thymocyte development and in peripheral T cell responses and activation. Shcbp1 is upregulated in thymocyte that are highly proliferative, and is further upregulated after anti-CD3 stimulation in both immature thymocytes and mature T cells. Our preliminary evidence suggests that Shcbp1 may help regulate the proliferative burst that occurs during ¿-selection, a developmental checkpoint that ensures proper expression and signaling through the TCR¿ chain. Additionally, our preliminary data suggests that Shcbp1 may regulate proliferation that occurs during the primary immune response. We will further investigate the role of Shcbp1 in T cell development and activation using a mouse with conditional deletion of Shcbp1 in the thymus, which will allow us to investigate the role of Shcbp1 in T cell development and peripheral T cell responses.