Immunology

Outnumbered, But Not Outgunned

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Science  21 Jul 2006:
Vol. 313, Issue 5785, pp. 275
DOI: 10.1126/science.313.5785.275c

During an immune response, cytotoxic T lymphocytes (CTLs) make contact with other cells in two ways: first, in the form of a stimulatory synapse, which requires prolonged interaction with an antigen-presenting cell or target cell to turn on effector functions in the CTL; and second, in a brisk-acting “lytic” synapse in which the intracellular weapons needed for the destruction of infected or transformed cells are rapidly brought to the contact site.

In order to explore the spatial and temporal relation of these functionally distinct kinds of synapse, Weidemann et al. mapped the kinetics of CTL-target cell interaction with the signatures of killing and CTL activation. When a CTL was seen to undertake a high-affinity encounter with an antigen-bearing target cell, a high threshold stimulatory synapse was formed and maintained, even after the target cell had been lysed. This suggests that sustained activation via prolonged contact with a relevant antigen is important for ongoing cytolytic activity. A CTL could simultaneously form short-lived lytic synapses with several other cells, but showed considerably less regard for antigen specificity in these interactions. Coordinating antigen-dependent activation with the rapid and simultaneous killing of multiple cells may help CTLs deal effectively with potentially overwhelming numbers of targets. — SJS

Proc. Natl. Acad. Sci. U.S.A. 103, 10985 (2006).

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