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  • 标题:Characterization of mechanisms positioning costimulatory complexes in immune synapses
  • 本地全文:下载
  • 作者:Anastasios Siokis ; Philippe A. Robert ; Philippos Demetriou
  • 期刊名称:iScience
  • 印刷版ISSN:2589-0042
  • 出版年度:2021
  • 卷号:24
  • 期号:10
  • 页码:1-21
  • DOI:10.1016/j.isci.2021.103100
  • 语种:English
  • 出版社:Elsevier
  • 摘要:SummarySmall 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.Graphical abstractDisplay OmittedHighlights•CD2-CD58 were passively excluded due to LFA-1 gradient and molecular crowding•CD2-CD58 short-range self-attraction induces corolla formation•CD2-CD58 and CD28-CD80 attraction induces a CD2-CD28 corolla•CD45 presence induces CD2-CD58 corolla formationCell biology; Computational bioinformatics; Computational molecular modelling; Immunology; Molecular biology
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