Metabolite antigens and pathway incompatibility.

Vgamma9Vdelta2 cells, which constitute a small portion of peripheral blood T-cells (approximately 5%), are known to be the biggest subset of human gammadelta T-cells ( approximately 70%) in circulating blood. The Vgamma9Vdelta2 T-cells expressing Vgamma9Vdelta2 T-cell receptors have an ability to recognize non-peptide antigens directly or indirectly, for example, phosphorylated metabolites referred to as phosphoantigens, synthesized aminobisphosphonates used for therapeutic purpose such as pamidronate, and alkylamines. These chemical compounds recognized by Vgamma9Vdelta2 T-cells are produced by many prokaryotic and eukaryotic organisms. Previous works show that the phosphoantigens recognized by Vgamma9Vdelta2 T-cells are found as the intermediates in the pathogens' pathway producing IPP. In this paper, we show that the other compounds recognized by Vgamma9Vdelta2 T-cells are found on the pathogens' biosynthetic pathways leading to production of shared compounds with human. In addition, many compounds having high structural similarity with alkylamine antigens are also found only in pathogen's biosynthetic pathways or produced only by non-human enzymes.