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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.

Original publication

DOI

10.1016/j.celrep.2018.06.114

Type

Journal article

Journal

Cell Rep

Publication Date

31/07/2018

Volume

24

Pages

1151 - 1162

Keywords

CD28, F-actin flow, agent-based modeling, immulogical synapse, molecular transport, pattern formation, Actins, Animals, B7-1 Antigen, CD28 Antigens, Computer Simulation, Humans, Immunological Synapses, Protein Transport, Signal Transduction