Structure-Activity Relationships of Butyrophilin 3 Ligands

Phosphoantigens (pAgs) are small phosphorus-containing molecules that stimulate V gamma 9V delta 2 T cells with sub-nanomolar cellular potency. Recent work has revealed that these compounds work through binding to the transmembrane immunoglobulin butyrophilin 3A1 (BTN3A1) within its intracellular B30.2 domain. Engagement of BTN3A1 is critical to the formation of an immune synapse between cells that contain pAgs and the V gamma 9V delta 2 T cells. This minireview summarizes the structure-activity relationships of pAgs and their implications to the mechanisms of butyrophilin 3 activation leading to V gamma 9V delta 2 T cell response.