ArticleThe Journal of experimental medicine2022
Systems-level conservation of the proximal TCR signaling network of mice and humans.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Ambient temperature regulates CD4iScience · 2026Article
- Disordered protein LAT encodes relative levels of signaling pathways in T cell activation.Science (New York, N.Y.) · 2026Article
- HIV Nef disrupts Lck signaling by inducing aberrant phosphorylation of its substrates.ImmunoHorizons · 2025Article
- Roles of TULA-family proteins in T cells and autoimmune diseases.Genes and immunity · 2025Review
- Low-avidity T cells drive endogenous tumor immunity in mice and humans.Nature immunology · 2025Article
- Defective LAT signalosome pathology in mice mimics human IgG4-related disease at single-cell level.The Journal of experimental medicine · 2023Article
- Numbers and odds: TCR repertoire size and its age changes impacting on T cell functions.Seminars in immunology · 2023Review
- Negative intracellular regulators of T-cell receptor (TCR) signaling as potential antitumor immunotherapy targets.Journal for immunotherapy of cancer · 2023Review
- Discrete LAT condensates encode antigen information from single pMHC:TCR binding events.Nature communications · 2022Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
We exploited traceable gene tagging in primary human T cells to establish the composition and dynamics of seven canonical TCR-induced protein signaling complexes (signalosomes) using affinity purification coupled with mass spectrometry (AP-MS). It unveiled how the LAT adaptor assembles higher-order molecular condensates and revealed that the proximal TCR-signaling network has a high degree of qualitative and quantitative conservation between human CD4+ and CD8+ T cells. Such systems-level conservation also extended across human and mouse T cells and unexpectedly encompassed protein-protein interaction stoichiometry. Independently of evolutionary considerations, our study suggests that a drug targeting the proximal TCR signaling network should behave similarly when applied to human and mouse T cells. However, considering that signaling differences likely exist between the distal TCR-signaling pathway of human and mouse, our fast-track AP-MS approach should be favored to determine the mechanism of action of drugs targeting human T cell activation. An opportunity is illustrated here using an inhibitor of the LCK protein tyrosine kinase as a proof-of-concept.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.