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White, J. T.

Publications and source records attributed to White, J. T..

2 recordsLinked to original sources

Thymically imprinted differential responsivity of naive CD4 T cells to IL2 results in a heterogeneity of both Treg induction and subsequent effector functioning

Thymic selection predisposes naive T cells to particular outcomes when challenged later with cognate antigen, whether the antigen is self or foreign. This suggests that there is an inherent heterogeneity of functioning among T cells within the naive population (both CD4 and CD8s), and that each T cell, as part of its thymic development, is given a certain programming which will affect its eventual fate decisions. In this project, we looked at the primary effects of this thymic imprinting on the conversion of naive CD4 T cells into Tregs. Further, using an induced-Treg-reporter system, we exam the impact of thymic imprinted heterogeneity on effector functionality and identity stability. We report that naive T cell differential responsivity to cytokines leads to the observed difference in Treg induction, and that the Tregs induced from T cells of different self-affinities maintain a heterogeneity of effector function and identity.

immunology↗

Tumor susceptibility gene-101 regulates glucocorticoid receptor through disorder-mediated allostery

Tumor Susceptibility Gene-101 (TSG101) is involved in endosomal maturation and has been implicated in the transcriptional regulation of several steroid hormone receptors (SHRs), although a detailed characterization of such regulation has yet to be conducted. Here we directly measure binding of TSG101 to one SHR, glucocorticoid receptor (GR). Using biophysical and cellular assays, we show that the coiled-coil domain of TSG101; 1) binds and folds the disordered N-terminal domain (NTD) of GR, 2) upon binding, improves DNA-binding of GR in vitro, and 3) enhances the transcriptional activity of GR in vivo. Our findings suggest that TSG101 is a bona fide transcriptional co-regulator of GR.

biophysics↗