Mevalonate-derived phosphonates bias γδ T cell activation toward BTN3A3
- Phosphonate versions of mevalonate diphosphate were made and tested for their ability to activate Vγ9Vδ2 T cells.
- Several analogs prompted interferon-γ release from effector cells, though none strongly expanded naive cells.
- The lead analog beat the natural metabolite, worked preferentially via BTN3A3-expressing cells, withstood statin treatment, and acted synergistically with a BTN3A1 agonist.
💡 Points Based on the abstract
Beating the natural metabolite while surviving statin treatment hints these phosphonates are not simply riding the mevalonate pathway, and the BTN3A3 bias is a new angle versus BTN3A1-centred phosphoantigen work. But charged diphosphate mimics have a classic permeability and stability problem. I'd ask how the lead behaves in cells without prodrugging.
Synthesis and Evaluation of Mevalonate Diphosphate Analogs as Butyrophilin 3A3 Ligands ↗