Initiation of T cell signaling by CD45 segregation at ‘close-contacts’

It has been proposed that the local segregation of kinases and the tyrosine phosphatase CD45 underpins T cell receptor (TCR) triggering, but how segregation would occur and whether it can initiate signaling is unclear. Using structural and biophysical analysis we show that the extracellular region o...

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Main Authors:	Chang, Veronica T, Fernandes, Ricardo A, Ganzinger, Kristina A, Lee, Steven F, Siebold, Christian, McColl, James, Jönsson, Peter, Palayret, Matthieu, Harlos, Karl, Coles, Charlotte H, Jones, E Yvonne, Lui, Yuan, Huang, Elizabeth, Gilbert, Robert J C, Klenerman, David, Aricescu, A Radu, Davis, Simon J
Format:	Online
Language:	English
Published:	2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839504/

id	pubmed-4839504
recordtype	oai_dc
spelling	pubmed-48395042016-09-22 Initiation of T cell signaling by CD45 segregation at ‘close-contacts’ Chang, Veronica T Fernandes, Ricardo A Ganzinger, Kristina A Lee, Steven F Siebold, Christian McColl, James Jönsson, Peter Palayret, Matthieu Harlos, Karl Coles, Charlotte H Jones, E Yvonne Lui, Yuan Huang, Elizabeth Gilbert, Robert J C Klenerman, David Aricescu, A Radu Davis, Simon J Article It has been proposed that the local segregation of kinases and the tyrosine phosphatase CD45 underpins T cell receptor (TCR) triggering, but how segregation would occur 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 new structures characterized by spontaneous sub-micron scale CD45 and kinase segregation, called ‘close-contacts’, initiates signaling even when TCR ligands are absent. Our work reveals the structural basis for, and the unexpectedly potent signaling effects of local CD45 and kinase segregation. TCR ligands could heighten signaling simply by holding receptors in close-contacts. 2016-03-21 2016-05 /pmc/articles/PMC4839504/ /pubmed/26998761 http://dx.doi.org/10.1038/ni.3392 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Chang, Veronica T Fernandes, Ricardo A Ganzinger, Kristina A Lee, Steven F Siebold, Christian McColl, James Jönsson, Peter Palayret, Matthieu Harlos, Karl Coles, Charlotte H Jones, E Yvonne Lui, Yuan Huang, Elizabeth Gilbert, Robert J C Klenerman, David Aricescu, A Radu Davis, Simon J
spellingShingle	Chang, Veronica T Fernandes, Ricardo A Ganzinger, Kristina A Lee, Steven F Siebold, Christian McColl, James Jönsson, Peter Palayret, Matthieu Harlos, Karl Coles, Charlotte H Jones, E Yvonne Lui, Yuan Huang, Elizabeth Gilbert, Robert J C Klenerman, David Aricescu, A Radu Davis, Simon J Initiation of T cell signaling by CD45 segregation at ‘close-contacts’
author_facet	Chang, Veronica T Fernandes, Ricardo A Ganzinger, Kristina A Lee, Steven F Siebold, Christian McColl, James Jönsson, Peter Palayret, Matthieu Harlos, Karl Coles, Charlotte H Jones, E Yvonne Lui, Yuan Huang, Elizabeth Gilbert, Robert J C Klenerman, David Aricescu, A Radu Davis, Simon J
author_sort	Chang, Veronica T
title	Initiation of T cell signaling by CD45 segregation at ‘close-contacts’
title_short	Initiation of T cell signaling by CD45 segregation at ‘close-contacts’
title_full	Initiation of T cell signaling by CD45 segregation at ‘close-contacts’
title_fullStr	Initiation of T cell signaling by CD45 segregation at ‘close-contacts’
title_full_unstemmed	Initiation of T cell signaling by CD45 segregation at ‘close-contacts’
title_sort	initiation of t cell signaling by cd45 segregation at ‘close-contacts’
description	It has been proposed that the local segregation of kinases and the tyrosine phosphatase CD45 underpins T cell receptor (TCR) triggering, but how segregation would occur 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 new structures characterized by spontaneous sub-micron scale CD45 and kinase segregation, called ‘close-contacts’, initiates signaling even when TCR ligands are absent. Our work reveals the structural basis for, and the unexpectedly potent signaling effects of local CD45 and kinase segregation. TCR ligands could heighten signaling simply by holding receptors in close-contacts.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839504/
_version_	1613568984267882496

Initiation of T cell signaling by CD45 segregation at ‘close-contacts’

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