Initiation of T cell signaling by CD45 segregation at 'close contacts'

Veronica T. Chang, Ricardo A. Fernandes, Kristina A. Ganzinger, Steven F. Lee, Christian Siebold, James McColl, Peter Jönsson, Matthieu Palayret, Karl Harlos, Charlotte H. Coles, E. Yvonne Jones, Yuan Lui, Elizabeth Huang, Robert J. C. Gilbert, David Klenerman, A. Radu Aricescu, Simon J. Davis

Research output: Contribution to journalArticlepeer-review

161 Citations (Scopus)

Abstract

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 languageEnglish
Pages (from-to)574–582
Number of pages9
JournalNature Immunology
Volume17
Early online date21 Mar 2016
DOIs
Publication statusPublished - May 2016

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