Loading...
F-Actin-Driven CD28-CD80 Localization in the Immune Synapse.
Siokis, Anastasios Robert, Philippe A Demetriou, Philippos Dustin, Michael L
Siokis, Anastasios
Robert, Philippe A
Demetriou, Philippos
Dustin, Michael L
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2018-07-31
Submitted date
Files
Loading...
Open Access publication
Adobe PDF, 4.37 MB
Other Titles
Abstract
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.
Citation
Cell Rep. 2018 Jul 31;24(5):1151-1162. doi: 10.1016/j.celrep.2018.06.114
Publisher
Journal
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
2211-1247
EISSN
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution-NonCommercial-ShareAlike 4.0 International