Metabolite Antigens and Pathway Incompatibility

Wataru Honda[1] (honda@kuicr.kyoto-u.ac.jp)
Shuichi Kawashima[2] (shuichi@hgc.jp)
Minoru Kanehisa[1],[2] (kanehisa@kuicr.kyoto-u.ac.jp)

[1]Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho Uji, Kyoto 611-0011, Japan
[2]Human Genome Center, Institute of Medical Science, University of Tokyo,4-6-1 Shirokane-dai Minato-ku, Tokyo 108-8639, Japan


Abstract

Vγ9Vδ2 cells, which constitute a small portion of peripheral blood T-cells (∼5%), are known to be the biggest subset of human γδ T-cells (∼70%) in circulating blood. The Vγ9Vδ2 T-cells expressing Vγ9Vδ2 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 Vγ9Vδ2 T-cells are produced by many prokaryotic and eukaryotic organisms. Previous works show that the phosphoantigens recognized by Vγ9Vδ2 T-cells are found as the intermediates in the pathogens' pathway producing IPP. In this paper, we show that the other compounds recognized by Vγ9Vδ2 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.

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Japanese Society for Bioinformatics