Immunology Different Synapses for Different Responses

Engagement of the T cell receptor can result in multiple cellular responses. For example, in immature T cells, this can produce positive selection or negative selection, which leads to apoptosis. Richie et al. developed a system using green fluorescent protein (GFP)-labeled components of the T cell signaling pathway to explore how the same signaling components can produce these disparate responses. Using the thymocytes that express fusion proteins between the T cell coreceptor CD3 or the tyrosine kinase Lck, the authors show that these two proteins accumulate at the site of cell:cell (thymocyte:stromal cell) interaction more efficiently under conditions of negative selection than conditions of positive selection. The organization of CD3 at the cell interface during negative selection was different than the organization of these proteins reported for mature T cell immune synapses. Time-lapse imaging of the GFP fusion proteins during immune synapse formation showed that synapse formation occurred quickly, that the labeled proteins were not immobilized within the synapse, and that the CD3 was predominantly excluded from the center of the synapse. This difference in geometry of the synapse may be one mechanism by which T cell responses can change during the course of development and in response to different T cell receptor stimuli.

L. I. Richie, P. J. R. Ebert, L. C. Wu, M. F. Krummel, J. J. T. Owen, M. M. Davis, Imaging synapse formation during thymocyte selection: Inability of CD3 to form a stable central accumulation during negative selection. Immunity 16, 595-606 (2002). [Online Journal]