Characterization of mechanisms positioning costimulatory complexes in immune synapses

Small immunoglobulin superfamily (sIGSF) adhesion complexes form a corolla of microdomains around an integrin ring and secretory core during immunological synapse (IS) formation. The corolla recruits and retains major costimulatory/checkpoint complexes, such as CD28, making forces that govern coroll...

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Huvudupphovsmän: Siokis, A, Robert, PA, Demetriou, P, Kvalvaag, A, Valvo, S, Mayya, V, Dustin, ML, Meyer-Hermann, M
Materialtyp: Journal article
Språk:English
Publicerad: Cell Press 2021
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author Siokis, A
Robert, PA
Demetriou, P
Kvalvaag, A
Valvo, S
Mayya, V
Dustin, ML
Meyer-Hermann, M
author_facet Siokis, A
Robert, PA
Demetriou, P
Kvalvaag, A
Valvo, S
Mayya, V
Dustin, ML
Meyer-Hermann, M
author_sort Siokis, A
collection OXFORD
description Small immunoglobulin superfamily (sIGSF) adhesion complexes form a corolla of microdomains around an integrin ring and secretory core during immunological synapse (IS) formation. The corolla recruits and retains major costimulatory/checkpoint complexes, such as CD28, making forces that govern corolla formation of particular interest. Here, we investigated the mechanisms underlying molecular reorganization of CD2, an adhesion and costimulatory molecule of the sIGSF family during IS formation. Computer simulations showed passive distal exclusion of CD2 complexes under weak interactions with the ramified F-actin transport network. Attractive forces between CD2 and CD28 complexes relocate CD28 from the IS center to the corolla. Size-based sorting interactions with large glycocalyx components, such as CD45, or short-range CD2 self-attraction successfully explain the corolla ‘petals.’ This establishes a general simulation framework for complex pattern formation observed in cell-bilayer and cell-cell interfaces, and the suggestion of new therapeutic targets, where boosting or impairing characteristic pattern formation can be pivotal.
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spelling oxford-uuid:21e276eb-b0c2-418f-8204-1715282e25812024-03-21T15:15:40ZCharacterization of mechanisms positioning costimulatory complexes in immune synapsesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:21e276eb-b0c2-418f-8204-1715282e2581EnglishSymplectic ElementsCell Press2021Siokis, ARobert, PADemetriou, PKvalvaag, AValvo, SMayya, VDustin, MLMeyer-Hermann, MSmall immunoglobulin superfamily (sIGSF) adhesion complexes form a corolla of microdomains around an integrin ring and secretory core during immunological synapse (IS) formation. The corolla recruits and retains major costimulatory/checkpoint complexes, such as CD28, making forces that govern corolla formation of particular interest. Here, we investigated the mechanisms underlying molecular reorganization of CD2, an adhesion and costimulatory molecule of the sIGSF family during IS formation. Computer simulations showed passive distal exclusion of CD2 complexes under weak interactions with the ramified F-actin transport network. Attractive forces between CD2 and CD28 complexes relocate CD28 from the IS center to the corolla. Size-based sorting interactions with large glycocalyx components, such as CD45, or short-range CD2 self-attraction successfully explain the corolla ‘petals.’ This establishes a general simulation framework for complex pattern formation observed in cell-bilayer and cell-cell interfaces, and the suggestion of new therapeutic targets, where boosting or impairing characteristic pattern formation can be pivotal.
spellingShingle Siokis, A
Robert, PA
Demetriou, P
Kvalvaag, A
Valvo, S
Mayya, V
Dustin, ML
Meyer-Hermann, M
Characterization of mechanisms positioning costimulatory complexes in immune synapses
title Characterization of mechanisms positioning costimulatory complexes in immune synapses
title_full Characterization of mechanisms positioning costimulatory complexes in immune synapses
title_fullStr Characterization of mechanisms positioning costimulatory complexes in immune synapses
title_full_unstemmed Characterization of mechanisms positioning costimulatory complexes in immune synapses
title_short Characterization of mechanisms positioning costimulatory complexes in immune synapses
title_sort characterization of mechanisms positioning costimulatory complexes in immune synapses
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