The early proximal αβ TCR signalosome specifies thymic selection outcome through a quantitative protein interaction network

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Science Immunology  15 Feb 2019:
Vol. 4, Issue 32, eaal2201
DOI: 10.1126/sciimmunol.aal2201

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Instructional signals for nascent T cells

Signals relayed through the TCR/CD3 complex are critical to determining whether immature T cells in the thymus undergo positive selection, enabling their survival and subsequent export to the periphery, or negative selection leading to death. Neier et al. developed a proteomics-based approach to profile proteins bound to the TCR/CD3 complex that enabled a comparison of differences between signaling associated with thymocyte survival versus death. They observed that the full range of cellular outcomes after thymic selection can be attributed to quantitative differences in a shared core set of biochemical signals. These findings indicate that differences in the affinity of TCRs for peptide-MHC complexes are transduced into downstream signals that are quantitatively variable but qualitatively similar.