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It has been proposed that the local segregation of kinases and the tyrosine phosphatase CD45 underpins T cell antigen receptor (TCR) triggering, but how such segregation occurs and whether it can initiate signaling is unclear. Using structural and biophysical analysis, we show that the extracellular region of CD45 is rigid and extends beyond the distance spanned by TCR-ligand complexes, implying that sites of TCR-ligand engagement would sterically exclude CD45. We also show that the formation of 'close contacts', new structures characterized by spontaneous CD45 and kinase segregation at the submicron-scale, initiates signaling even when TCR ligands are absent. Our work reveals the structural basis for, and the potent signaling effects of, local CD45 and kinase segregation. TCR ligands have the potential to heighten signaling simply by holding receptors in close contacts.

Original publication

DOI

10.1038/ni.3392

Type

Journal article

Journal

Nat Immunol

Publication Date

05/2016

Volume

17

Pages

574 - 582

Keywords

Antigens, CD45, Crystallography, X-Ray, HEK293 Cells, Humans, Jurkat Cells, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Microscopy, Electron, Microscopy, Fluorescence, Models, Molecular, Protein Structure, Tertiary, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Time Factors, ZAP-70 Protein-Tyrosine Kinase