Journal article
The early proximal TCR signalosome specifies thymic selection outcome through a quantitative protein interaction network
SC Neier, A Ferrer, KM Wilton, SEP Smith, AMH Kelcher, KD Pavelko, JM Canfield, TR Davis, RJ Stiles, Z Chen, J McCluskey, SR Burrows, J Rossjohn, DM Hebrink, EM Carmona, AH Limper, DJ Kappes, PJ Wettstein, AJ Johnson, LR Pease Show all
Science Immunology | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2019
Abstract
During T cell development, T cell antigen receptor (TCR) engagement transduces biochemical signals through a protein-protein interaction (PPI) network that dictates dichotomous cell fate decisions. It remains unclear how signal specificity is communicated, instructing either positive selection to advance cell differentiation or death by negative selection. Early signal discrimination might occur by PPI signatures differing qualitatively (customized, unique PPI combinations for each signal), quantitatively (graded amounts of a single PPI series), or kinetically (speed of PPI pathway progression). Using a novel PPI network analysis, we found that early TCR-proximal signals distinguishing posit..
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Awarded by Mayo Foundation for Medical Education and Research
Funding Acknowledgements
This work was supported by the University of Missouri-Columbia and the Mayo Foundation (to D.G. and A.G.S.); NIH grants R01GM103841 (to A.G.S.), R01AI097187 (to D.G.), and R21NS094765 (to A.J.J.); BD Biosciences Research Award (to A.G.S.); NIH training grants T32AI7425 and T32AI007386 (to S.C.N.) and T32GM65841 (to K.M.W.); Consortium of Multiple Sclerosis Centers Foundation Student Research Scholarship Program (to K.M.W.); and the generous philanthropic partnership of B. Fineman with the Mayo Clinic (to A.G.S.).