The B7 family protein butyrophilin 3A1 (BTN3A1) is an immune co-receptor that binds intracellular pathogen-derived molecules such as (<i>E</i>)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) leading to a unique inside-out transmembrane signaling event. Receptor binding to these ligands promotes a multifaceted immune response including activation of Vgamma9Vdelta2 T cells. To further understand the underlying structure activity relationships, we have examined a number of novel butyrophilin ligands and their prodrugs. The prodrugs stimulate T cell effector functions with low nanomolar activity that is fully dependent upon cellular expression of BTN3A1. Furthermore, these compounds have enabled insights into the mechanisms of BTN3A1 cross-membrane signaling, including a dependence on intracellular ligand binding, induction of an intracellular domain conformational change, and the potential for cooperativity at the cellular level.

Immune modulation by butyrophilin ligands and their prodrugs

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.