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Organisation of T cell signalling

Understanding how protein interaction is deregulated during disease represents a major challenge. European scientists examined the role of protein spatial organisation in protein function using a novel microscopy approach.
Organisation of T cell signalling
Cellular activation occurs through complex signalling networks that involve numerous proteins. Normally, proteins that are closely positioned within a cell interact together. However, proteins enrich at particular locations and times within cells, enhancing their interaction efficiency. At the systems scale, such patterning determines how regulatory information flows through signalling networks.

Delineating the functional integration of groups of proteins would provide important insight into cell function under physiological and pathological conditions including autoimmunity and cancer. Towards this goal, scientists of the EU-funded T CELL SIGNALING (The spatiotemporal organisation of T cell signalling as a regulator of T cell function) project developed unique approaches to visualise signalling as it occurs inside live primary cells in time and space. They employed live cell time-lapse fluorescence microscopy to study the activation of primary T cells, the central regulators of immune responses.

Computational image analysis was integrated in the approach alongside electron microscopy to provide higher spatial resolution. In addition, mathematical modelling enabled the analysis of complex signalling systems.

This method was employed to address important scientific questions such as regulation of T cell activation with an emphasis on the actin cytoskeleton. Researchers wanted to elucidate how the spatiotemporal organisation of T cell signalling regulates lymphocyte function. In this context, they followed the spatiotemporal localisation of the tyrosine kinases Itk and Tec in cytokine secretion and primary immunodeficiency. Expression of the central costimulatory receptor CD28 was also visualised in cytotoxic T cells and natural killer cells alongside SLAM receptors to determine their role in the autoimmune disease systemic lupus erythematosus.

Additional applications of the approach included the studying of T cell signalling in a murine model of multiple sclerosis and in tumour-infiltrating lymphocytes as well as the characterisation of a pharmaceutical lead compound.

Taken together, the T CELL SIGNALING approach offered an important tool for observing the location of proteins within cells over time. The applications of this method extend beyond the immune system and could help unveil the intricate signalling pathways that drive cell function.

Related information

Subjects

Life Sciences

Keywords

T cell, signalling, protein, microscopy, T CELL SIGNALING, spatiotemporal organisation
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