AT cell coreceptor keeps T cells moving so that they are not overactivated, according to Helga Schneider, Christopher Rudd (University of Cambridge, UK), and colleagues. By not lingering too long, killer T cells might be at their most efficient.
Rudd's group recently found that this coreceptor, called CTLA-4, was needed for integrin activation. Integrins go hand-in-hand with cell migration, which the authors now show is increased by CTLA-4 engagement.
When T cells meet the right antigen-presenting cell (APC), they normally stop and interact with the APC to get activated. This stopping phase, the authors show, is limited by CTLA-4, which is found on all activated T cells and binds to ligands on the APC.
By restricting the interaction time, CTLA-4 may prevent responses to low-affinity self-antigens that cause autoimmunity. This idea is supported by the severe autoimmunity found in mice lacking CTLA-4. Rudd suspects that their T cells “park next to an APC for so long that they start accumulating signals against self-antigens.”
The anti–stop signal might have been designed to make cytotoxic T cells more efficient in killing infected or cancerous cells. It might also explain why anti–CTLA-4 antibodies succeed as cancer therapies, if they act as ligand mimics. “The release of [cytotoxic] granzymes is relatively quick,” says Rudd. “The T cell can kill the tumor target cell and not stick around any longer than it needs to, take off again and encounter another target.”