F-actin-driven CD28-CD80 localization in the immune synapse
During immunological synapse (IS) formation, T cell receptor (TCR) signaling complexes, integrins, and costimulatory molecules exhibit a particular spatial localization. Here, we develop an agent-based model for the IS formation based on TCR peptide-bound major histocompatibility complex (pMHC) and...
| Glavni autori: | , , , , |
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| Format: | Journal article |
| Jezik: | English |
| Izdano: |
Elsevier
2018
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| _version_ | 1826289349951488000 |
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| author | Siokis, A Robert, P Demetriou, P Dustin, M Meyer-Hermann, M |
| author2 | Dustin, M |
| author_facet | Dustin, M Siokis, A Robert, P Demetriou, P Dustin, M Meyer-Hermann, M |
| author_sort | Siokis, A |
| collection | OXFORD |
| description | During immunological synapse (IS) formation, T cell receptor (TCR) signaling complexes, integrins, and costimulatory molecules exhibit a particular spatial localization. Here, we develop an agent-based model for the IS formation based on TCR peptide-bound major histocompatibility complex (pMHC) and leukocyte-function-associated antigen 1 (LFA-1) intracellular activation molecule 1 (ICAM-1) dynamics, including CD28 binding to a costimulatory ligand, coupling of molecules to the centripetal actin flow, and size-based segregation (SBS). A radial gradient of LFA-1 in the peripheral supramolecular activation cluster (pSMAC) toward the central supramolecular activation cluster (cSMAC) emerged as a combined consequence of actin binding and diffusion and modified the positioning of other molecules. The simulations predict a mechanism of CD28 movement, according to which CD28-CD80 complexes passively follow TCR-pMHC microclusters. However, the characteristic CD28-CD80 localization in a ring pattern around the cSMAC only emerges with a particular CD28-actin coupling strength that induces a centripetal motion. These results have implications for the understanding of T cell activation and fate decisions. |
| first_indexed | 2024-03-07T02:27:32Z |
| format | Journal article |
| id | oxford-uuid:a620fc13-64f3-4b7e-950d-8be94c0ffb0c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:27:32Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:a620fc13-64f3-4b7e-950d-8be94c0ffb0c2022-03-27T02:45:04ZF-actin-driven CD28-CD80 localization in the immune synapseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a620fc13-64f3-4b7e-950d-8be94c0ffb0cEnglishSymplectic Elements at OxfordElsevier2018Siokis, ARobert, PDemetriou, PDustin, MMeyer-Hermann, MDustin, MDuring immunological synapse (IS) formation, T cell receptor (TCR) signaling complexes, integrins, and costimulatory molecules exhibit a particular spatial localization. Here, we develop an agent-based model for the IS formation based on TCR peptide-bound major histocompatibility complex (pMHC) and leukocyte-function-associated antigen 1 (LFA-1) intracellular activation molecule 1 (ICAM-1) dynamics, including CD28 binding to a costimulatory ligand, coupling of molecules to the centripetal actin flow, and size-based segregation (SBS). A radial gradient of LFA-1 in the peripheral supramolecular activation cluster (pSMAC) toward the central supramolecular activation cluster (cSMAC) emerged as a combined consequence of actin binding and diffusion and modified the positioning of other molecules. The simulations predict a mechanism of CD28 movement, according to which CD28-CD80 complexes passively follow TCR-pMHC microclusters. However, the characteristic CD28-CD80 localization in a ring pattern around the cSMAC only emerges with a particular CD28-actin coupling strength that induces a centripetal motion. These results have implications for the understanding of T cell activation and fate decisions. |
| spellingShingle | Siokis, A Robert, P Demetriou, P Dustin, M Meyer-Hermann, M F-actin-driven CD28-CD80 localization in the immune synapse |
| title | F-actin-driven CD28-CD80 localization in the immune synapse |
| title_full | F-actin-driven CD28-CD80 localization in the immune synapse |
| title_fullStr | F-actin-driven CD28-CD80 localization in the immune synapse |
| title_full_unstemmed | F-actin-driven CD28-CD80 localization in the immune synapse |
| title_short | F-actin-driven CD28-CD80 localization in the immune synapse |
| title_sort | f actin driven cd28 cd80 localization in the immune synapse |
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