Lauffenburger:Megan Palmer

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Megan Palmer (BE doctoral)

Integration of T Cell Receptor and Interleukin 7 Cytokine Signaling for Network Control of Naïve CD8+ T Cell Fate

The transfer of naïve T cells into lymphopenic hosts results in their proliferation and differentiation to a memory phenotype. Lymphopenia-induced proliferation is critical to reconstitution of the immune system following T cell depletion by viral immunodeficiency or chemotherapy, and provides insight into the mechanisms of T cell maintenance. T cell survival and proliferation is dependent upon T cell receptor (TCR) stimulation by self-peptide/major histocompatibility complex (spMHC) in combination with cytokine signaling by interleukin-7 (IL-7) through the IL-7 receptor (IL-7R). IL-7R and TCR stimuli are thought to act synergistically in their regulation of T cell expansion. However, the mechanisms of signaling cross-talk are not known.

To elucidate how TCR and IL-7R signals direct cellular responses, we are developing an in vitro system to enable controlled TCR and IL-7R stimulation. Dynamic signaling activities across common downstream pathways will be simultaneously measured alongside phenotypic responses to characterize network behavior governing distinct T cell fates. Statistical and/or probabilistic modeling approaches will be used to derive from these portraits of signaling behavior predicted mechanisms of regulation and synergy in the TCR-IL7 network.