Imaging Synapse Formation during Thymocyte Selection: Inability of CD3ζ to Form a Stable Central Accumulation during Negative Selection

TCR signaling can result in cell fates ranging from activation to tolerance to apoptosis. Organization of molecules in an “immunological synapse” between mature T cells and APCs correlates with the strength of TCR signaling. To investigate synapse formation during thymic selection, we have establish...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2002-04, Vol.16 (4), p.595-606
Main Authors: Richie, Lauren I., Ebert, Peter J.R., Wu, Lawren C., Krummel, Matthew F., Owen, John J.T., Davis, Mark M.
Format: Article
Language:English
Subjects:
CD3 antigen
lck protein
p56 protein
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Summary:TCR signaling can result in cell fates ranging from activation to tolerance to apoptosis. Organization of molecules in an “immunological synapse” between mature T cells and APCs correlates with the strength of TCR signaling. To investigate synapse formation during thymic selection, we have established a reaggregate system in which molecular recruitment of GFP fusion proteins to thymocyte:stromal cell interfaces can be visualized in real time. We demonstrate that negative selection is associated with efficient conjugate formation and rapid recruitment of p56 lck and CD3ζ to an immunological synapse. Interestingly, CD3ζ-GFP does not accumulate at the center of the synapse, as in mature T cells, but at the periphery across a wide range of ligand densities. This implicates differences in synapse geometry in initiation of alternate signals downstream of the TCR.
ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(02)00299-6