Metabolite Antigens and Pathway Incompatibility

Abstract

Vγ9Vδ2 cells, which constitute a small portion of peripheral blood T-cells (-5%), are knownto be the biggest subset of human γδ T-cells (-70%) in circulating blood. The Vγ9Vδ2 T-cellsexpressing Vγ9Vδ2 T-cell receptors have an ability to recognize non-peptide antigens directly orindirectly, for example, phosphorylated metabolites referred to as phosphoantigens, synthesizedaminobisphosphonates used for therapeutic purpose such as pamidronate, and alkylamines. Thesechemical compounds recognized by Vγ9Vδ2 T-cells are produced by many prokaryoticand eukaryoticorganisms. Previous works show that the phosphoantigens recognized by Vγ9Vδ2 T-cells arefound as the intermediates in the pathogens' pathway producing IPP. In this paper, we show thatthe other compounds recognized by Vγ9Vδ2 T-cells are found on the pathogens' biosynthetic pathwaysleading to production of shared compounds with human. In addition, many compounds havinghigh structural similarity with alkylamine antigens are also found only in pathogen's biosynthetic pathways or produced only by non-human enzymes.