During immunological synapse (IS) formation, T cell receptor (TCR) signaling complexes, integrins, as well as costimulatory and inhibitory molecules exhibit characteristic spatial localization. The IS is built around a TCR-peptide-major histocompatibility complex (pMHC) core, and is surrounded by an integrin ring (Monks, et al., 1998). Small immunoglobulin superfamily (sIGSF) adhesion complexes form a corolla of microdomains outside the integrin ring, which is shown to recruit and retain the major costimulatory and checkpoint complexes that regulate the responses to TCR engagement (Demetriou, et al., 2020). The positioning of these molecules drives T cell signaling and fate decision, making forces that govern IS formation of particular interest.
To gain insights into the mechanisms underlying molecular reorganization and characteristic pattern formation during IS formation, we developed a general agent-based simulation platform able to test different hypotheses.
The simulations identify several key biological interactions.
This work establishes a general simulation framework that can recapitulate complex pattern formation processes observed in cell-bilayer and cell-cell interfaces. The presented results have implications for the understanding of T cell activation and fate decision.