Tumor-Associated Phosphoantigen (PAg)

Tumor-associated phosphoantigens (PAgs) are small, phosphorylated non-peptide metabolites that accumulate in cells due to aberrant metabolic activity, such as that found in tumor cells or during microbial infection. These molecules are recognized by a specific subset of human γδ T lymphocytes—primarily those expressing the Vγ9Vδ2 T cell receptor (TCR). The most well-characterized phosphoantigens include isopentenyl pyrophosphate (IPP), which accumulates via the mevalonate pathway in tumor cells, and (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), produced by microbes. PAgs act as potent activators of Vγ9Vδ2 T cells, leading to cytotoxicity and cytokine release. PAg recognition is mediated by butyrophilin proteins, BTN3A1 and BTN2A1.

Other names

PhosphoantigenPAgsIPP (Isopentenyl pyrophosphate)HMBPP ((E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate)

Activation of Vγ9Vδ2 T cells via BTN3A1/BTN2A1 presentation complex.