Sci. Signal., 15 October 2013
Thymocytes Make a Deadly StopThymocytes are T cell precursors that develop in the thymus. To ensure that mature T cells discriminate appropriately between self-antigens and foreign antigens, thymocytes undergo selection initiated by the presentation of self-peptides by antigen-presenting cells to the T cell receptor (TCR) on the thymocyte (see the Perspective by Brzostek and Gascoigne). Relatively weak TCR signaling ensures thymocyte survival (positive selection); however, strong TCR signaling results in thymocyte death (negative selection). Melichar et al. performed two-photon imaging of fluorescently labeled mouse thymocytes on thymic slices containing various antigenic peptides to simultaneously monitor thymocyte migration and the extent of intracellular Ca2+ signaling. Positive selection was characterized by migratory thymocytes with decreased Ca2+ signaling, whereas negative selection was characterized by migratory arrest and enhanced Ca2+ signaling, suggesting that transient TCR signaling without migratory arrest is required for thymocyte survival and development.
Citation: H. J. Melichar, J. O. Ross, P. Herzmark, K. A. Hogquist, E. A. Robey, Distinct Temporal Patterns of T Cell Receptor Signaling During Positive Versus Negative Selection in Situ. Sci. Signal. 6, ra92 (2013).
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