Characterization of mechanisms positioning costimulatory complexes in immune synapses
Anastasios Siokis,
Philippe A. Robert,
Philippos Demetriou,
Audun Kvalvaag,
Salvatore Valvo,
Viveka Mayya,
Michael L. Dustin,
Michael Meyer-Hermann
Affiliations
Anastasios Siokis
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig 38106, Germany
Philippe A. Robert
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig 38106, Germany
Philippos Demetriou
Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7FY, UK
Audun Kvalvaag
Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7FY, UK; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0379 Oslo, Norway
Salvatore Valvo
Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7FY, UK
Viveka Mayya
Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7FY, UK
Michael L. Dustin
Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7FY, UK; Corresponding author
Michael Meyer-Hermann
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig 38106, Germany; Institute of Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Braunschweig 38106, Germany; Corresponding author
Summary: 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.
