Sensing cell stress and transformation through Vγ9Vδ2 T cell-mediated recognition of the isoprenoid pathway metabolites

Vγ9Vδ2 cells, a major peripheral blood γδ T cell subset in adults, recognize non-peptidic phosphorylated metabolites referred to as phosphoantigens (phosphoAg), which are produced by a broad array of prokaryotic and eukaryotic organisms. We will review here the biosynthetic pathways leading to production of phosphoAg and our current understanding of the mode of activation of Vγ9Vδ2 cells by these compounds. We will also discuss the physiological relevance of this immune recognition process and show how it can enable discrimination by Vγ9Vδ2 lymphocytes of infected and/or transformed cells.