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.”


Schneider, H., et al. 2006. Science. doi: