The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells.

The interaction between a T cell and an antigen-presenting cell (APC) can trigger a signaling response that leads to T cell activation. Prior studies have shown that ligation of the T cell receptor (TCR) triggers a signaling cascade that proceeds through the coalescence of TCR and various signaling...

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Main Authors: Kaizuka, Y, Douglass, A, Vardhana, S, Dustin, M, Vale, R
Format: Journal article
Language:English
Published: 2009
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author Kaizuka, Y
Douglass, A
Vardhana, S
Dustin, M
Vale, R
author_facet Kaizuka, Y
Douglass, A
Vardhana, S
Dustin, M
Vale, R
author_sort Kaizuka, Y
collection OXFORD
description The interaction between a T cell and an antigen-presenting cell (APC) can trigger a signaling response that leads to T cell activation. Prior studies have shown that ligation of the T cell receptor (TCR) triggers a signaling cascade that proceeds through the coalescence of TCR and various signaling molecules (e.g., the kinase Lck and adaptor protein LAT [linker for T cell activation]) into microdomains on the plasma membrane. In this study, we investigated another ligand-receptor interaction (CD58-CD2) that facilities T cell activation using a model system consisting of Jurkat T cells interacting with a planar lipid bilayer that mimics an APC. We show that the binding of CD58 to CD2, in the absence of TCR activation, also induces signaling through the actin-dependent coalescence of signaling molecules (including TCR-zeta chain, Lck, and LAT) into microdomains. When simultaneously activated, TCR and CD2 initially colocalize in small microdomains but then partition into separate zones; this spatial segregation may enable the two receptors to enhance signaling synergistically. Our results show that two structurally distinct receptors both induce a rapid spatial reorganization of molecules in the plasma membrane, suggesting a model for how local increases in the concentration of signaling molecules can trigger T cell signaling.
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spelling oxford-uuid:9816cf8a-45dc-422e-ac2e-ea3b840c42842022-03-27T00:04:34ZThe coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9816cf8a-45dc-422e-ac2e-ea3b840c4284EnglishSymplectic Elements at Oxford2009Kaizuka, YDouglass, AVardhana, SDustin, MVale, RThe interaction between a T cell and an antigen-presenting cell (APC) can trigger a signaling response that leads to T cell activation. Prior studies have shown that ligation of the T cell receptor (TCR) triggers a signaling cascade that proceeds through the coalescence of TCR and various signaling molecules (e.g., the kinase Lck and adaptor protein LAT [linker for T cell activation]) into microdomains on the plasma membrane. In this study, we investigated another ligand-receptor interaction (CD58-CD2) that facilities T cell activation using a model system consisting of Jurkat T cells interacting with a planar lipid bilayer that mimics an APC. We show that the binding of CD58 to CD2, in the absence of TCR activation, also induces signaling through the actin-dependent coalescence of signaling molecules (including TCR-zeta chain, Lck, and LAT) into microdomains. When simultaneously activated, TCR and CD2 initially colocalize in small microdomains but then partition into separate zones; this spatial segregation may enable the two receptors to enhance signaling synergistically. Our results show that two structurally distinct receptors both induce a rapid spatial reorganization of molecules in the plasma membrane, suggesting a model for how local increases in the concentration of signaling molecules can trigger T cell signaling.
spellingShingle Kaizuka, Y
Douglass, A
Vardhana, S
Dustin, M
Vale, R
The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells.
title The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells.
title_full The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells.
title_fullStr The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells.
title_full_unstemmed The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells.
title_short The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells.
title_sort coreceptor cd2 uses plasma membrane microdomains to transduce signals in t cells
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