Study of dynamics of T cell signaling published in Science Signaling

CPCB alum Dr. Taraz Buck and current CPCB student Xiongtao Ruan, were co-first authors of a collaboration between Carnegie Mellon and the University of Bristol resulting in a major recent paper in Science Signaling.

Cells often need to respond to signals received through surface receptors, and their responses involve changes in the spatial arrangement of proteins with the cell. For example, T cells receive signals through the T cell receptor (TCR) to indicate the presence of a particular antigen that they should respond to, and an additional signal through a costimulatory receptor (CD28) is required for them to respond fully.

Changes in individual proteins within the T cell can be imaged using fluorescence microscopy, but variability from cell to cell and noise in the images make it difficult to understand the sequence of events that are occurring. Buck, Ruan and other members of Dr. Murphy’s group developed computational methods to address this problem, collaborating with the group of Dr. Christoph Wülfing at the University of Bristol who imaged fluorescently-tagged signaling proteins in T cells activated through the TCR in the absence or presence of CD28 signaling. The results was detailed “maps” of the concentration of nine proteins over time following stimulation (see movie below). The computational analysis method could be combined with imaging of other signaling systems to provide more detailed understanding of their dynamics. The work was part of the activities of the NIH-supported National Center for Multiscale Modeling of Biological Systems.

Each frame of the movie depicts the distribution of cofilin (red), MRLC (green), and WAVE2 (blue) in slices perpendicular (top) or parallel (bottom) to the immunological synapse (where the signaling is occuring ). Voxels containing more than one protein are shown in composite colors. Note that the three proteins have different distributions before stimulation, that cofilin and WAVE2 are the first to arrive at the synapse (as indicated by the presence of magenta), that MRLC is added later (indicated by the synapse region turning white), and that this is followed by cofilin and WAVE2 leaving the synapse in sequence.