ArticleProceedings of the National Academy of Sciences of the United States of America2017
In vitro reconstitution of T cell receptor-mediated segregation of the CD45 phosphatase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 101 citations in OpenAlex.
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- T cell engagers control solid tumors through clonal replacement and IL2-driven effector differentiation of CD8 T cells.bioRxiv : the preprint server for biology · 2026Article
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- Geometric parameters that affect the behavior of logic-gated CAR T cells.Frontiers in immunology · 2024Article
- T-cell virtuosity in ''knowing thyself".Frontiers in immunology · 2024Review
- MAxSIM: multi-angle-crossing structured illumination microscopy with height-controlled mirror for 3D topological mapping of live cells.Communications biology · 2023Article
- CD45RA and CD45RO Are Regulated in a Cell-Type Specific Manner in Inflammation and Sepsis.Cells · 2023Article
- T Cell engineering for cancer immunotherapy by manipulating mechanosensitive force-bearing receptors.Frontiers in bioengineering and biotechnology · 2023Review
- Observing Membrane and Cell Adhesion via Reflection Interference Contrast Microscopy.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Size-dependent activation of CAR-T cells.Science immunology · 2022Article
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- Simulation of receptor triggering by kinetic segregation shows role of oligomers and close contacts.Biophysical journal · 2022Article
- Trapping or slowing the diffusion of T cell receptors at close contacts initiates T cell signaling.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
T cell signaling initiates upon the binding of peptide-loaded MHC (pMHC) on an antigen-presenting cell to the T cell receptor (TCR) on a T cell. TCR phosphorylation in response to pMHC binding is accompanied by segregation of the transmembrane phosphatase CD45 away from TCR-pMHC complexes. The kinetic segregation hypothesis proposes that CD45 exclusion shifts the local kinase-phosphatase balance to favor TCR phosphorylation. Spatial partitioning may arise from the size difference between the large CD45 extracellular domain and the smaller TCR-pMHC complex, although parsing potential contributions of extracellular protein size, actin activity, and lipid domains is difficult in living cells. Here, we reconstitute segregation of CD45 from bound receptor-ligand pairs using purified proteins on model membranes. Using a model receptor-ligand pair (FRB-FKBP), we first test physical and computational predictions for protein organization at membrane interfaces. We then show that the TCR-pMHC interaction causes partial exclusion of CD45. Comparing two developmentally regulated isoforms of CD45, the larger R
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