Lytic granules (blue) insert between the signaling patch (red) and the adhesion ring (green).

Griffiths/Elsevier

CD8 cytotoxic T cells are serial killers that slay one infected or cancerous cell after another. During each fatal encounter, an intercellular junction called the immunological synapse forms between killer and victim, according to researchers from Oxford University (Oxford, UK). Their work suggests new functions for the immunological synapse and supports the hypothesis that the immune system governs the number of cytotoxic T cells by “retiring” veterans of multiple battles.

In earlier studies immunological synapses were spotted only when an antigen- presenting cell met and activated a CD4 T cell. Although a CD8 cytotoxic T cell may attach to its victim for as little as two minutes, Gillian Griffiths and colleagues observed that synapses also formed during these contacts. The synapses have the characteristic bull's eye structure of a ring of adhesion proteins surrounding a ring of signaling proteins. The authors also showed that the cell-killing granules released by the cytotoxic T lymphocyte emerged from a focused secretory domain within the adhesion domain.The immunological synapse was thought to provide sustained signaling. But the new results suggest that the architecture of the synapse may help guide the secretion of molecules and prevent the death of nearby bystander cells, Griffiths says. She adds that the synapse may also participate in regulating the numbers of cytotoxic T cells. As the two cells part, the T cell picks up some of the victim's proteins, probably by ripping off a hunk of membrane. Thus, the T cells end up looking more and more like their targets, leading them to destroy each other in a phenomenon called fratricide. ▪

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