Spatial and temporal correlation of signals in t lymphocyte activation

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Project objective

The aim of this interdisciplinary project is the development of a data-driven mathematical model describing the signaling properties of the immunological synapse. The immunological synapse formed between a T cell and an antigen presenting cell is a highly organized state comprising an enormous amount of T cell surface molecules such as the T cell receptor, adhesion molecules (ICAM1, LFA-1) and signaling related molecules (CD2, CD45) . We believe that the spatial organization of the molecules at the interface between T cell and antigen presenting cell plays a key role in antigen recognition. Organizing the T cell receptors ill a synapse results via serial triggering of many T cell receptors in temporal and spatial correlation of signaling events. We will combine numerical data-analysis with mathematical modeling to study this concept mathematically. Numerical data-analysis will use proper orthogonal decomposition and time series analysis. Building on the results of the data-analysis, a mathematical model of the immunological synapse will be developed. The first step in mathematical modeling will be a compartment model of the synapse which will be extended to a detailed spatial model using either partial differential equations or a lattice model (depending on the results of the data-analysis). Such a model will allow us to analyze the correlation of signaling events in the synapse which will explain how transient T cell receptor engagement yields a sustained signal.

Original text from CORDIS.

Participants

• INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · PARISCoordinatorFrance

Links

• View on CORDIS