ArticleScience immunology2019
The early proximal αβ TCR signalosome specifies thymic selection outcome through a quantitative protein interaction network.
Article in Science immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Dissociation of the mTOR Protein Interaction Network Following Neuronal Activation Is Altered by Shank3 Mutation.Journal of neurochemistry · 2026Article
- SRC family kinase inhibition rescues molecular and behavioral phenotypes, but not protein interaction network dynamics, in a mouse model of Fragile X syndrome.Molecular psychiatry · 2024Article
- Differential protein-protein interactions underlie signaling mediated by the TCR and a 4-1BB domain-containing CAR.Science signaling · 2024Article
- Protein interaction network analysis of mTOR signaling reveals modular organization.bioRxiv : the preprint server for biology · 2023Article
- Fetal Thymic Organ Culture and Negative Selection.Methods in molecular biology (Clifton, N.J.) · 2023Article
- In Vitro Analysis of Thymocyte Signaling.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Early expression of mature αβ TCR in CD4Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Synaptic protein interaction networks encode experience by assuming stimulus-specific and brain-region-specific states.Cell reports · 2021Article
- Public and private human T-cell clones respond differentially to HCMV antigen when boosted by CD3 copotentiation.Blood advances · 2020Article
- FOLFOX Chemotherapy Ameliorates CD8 T Lymphocyte Exhaustion and Enhances Checkpoint Blockade Efficacy in Colorectal Cancer.Frontiers in oncology · 2020Article
- Quantification of Protein Interaction Network Dynamics using Multiplexed Co-Immunoprecipitation.Journal of visualized experiments : JoVE · 2019Article
- Synaptic activity induces input-specific rearrangements in a targeted synaptic protein interaction network.Journal of neurochemistry · 2018Article
Corrections and comments
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Authors and funding
24 authors at 7 institutions in 3 countries.
Funding
Abstract
During αβ 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 positive from negative selection appeared to be primarily quantitative in nature. Furthermore, the signal intensity of this PPI network was used to find an antigen dose that caused a classic negative selection ligand to induce positive selection of conventional αβ T cells, suggesting that the quantity of TCR triggering was sufficient to program selection outcome. Because previous work had suggested that positive selection might involve a qualitatively unique signal through CD3δ, we reexamined the block in positive selection observed in CD3δ
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