CTLA-4: Acting at the Synapse

Abstract

Egen and Allison have reported that cytotoxic T lymphocyte antigen-4 (CTLA-4), an immune-response–inhibiting protein, accumulates in a two-step process at immune synapses (the sites of physical contact between T cells and antigen-presenting cells). Depending upon the strength of the signal through the T cell receptor (TCR), CTLA-4 may reside at a cytoplasmic location near the synapse (in instances of weaker stimulation) or localize to the synapse itself (under strong TCR signaling conditions). Chikuma and Bluestone discuss these findings and how CTLA-4 might inhibit T cell activation, either by increasing the threshold for activation, or by dampening existing immune responses. These findings also have important ramifications for autoimmunity and the breadth of T cell proliferation (diverse vs. narrow clonal expansion) in immune responses.