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An Update on the Molecular Basis of Phosphoantigen Recognition by Vγ9Vδ2 T Cells

1
Institute for Virology and Immunobiology, Department of Medicine, University of Wuerzburg, 97070 Wuerzburg, Germany
2
Institute of Immunology, Hannover Medical School, 30559 Hannover, Germany
*
Author to whom correspondence should be addressed.
Cells 2020, 9(6), 1433; https://doi.org/10.3390/cells9061433
Received: 15 May 2020 / Revised: 5 June 2020 / Accepted: 6 June 2020 / Published: 9 June 2020
About 1–5% of human blood T cells are Vγ9Vδ2 T cells. Their hallmark is the expression of T cell antigen receptors (TCR) whose γ-chains contain a rearrangement of Vγ9 with JP (TRGV9JP or Vγ2Jγ1.2) and are paired with Vδ2 (TRDV2)-containing δ-chains. These TCRs respond to phosphoantigens (PAg) such as (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), which is found in many pathogens, and isopentenyl pyrophosphate (IPP), which accumulates in certain tumors or cells treated with aminobisphosphonates such as zoledronate. Until recently, these cells were believed to be restricted to primates, while no such cells are found in rodents. The identification of three genes pivotal for PAg recognition encoding for Vγ9, Vδ2, and butyrophilin (BTN) 3 in various non-primate species identified candidate species possessing PAg-reactive Vγ9Vδ2 T cells. Here, we review the current knowledge of the molecular basis of PAg recognition. This not only includes human Vγ9Vδ2 T cells and the recent discovery of BTN2A1 as Vγ9-binding protein mandatory for the PAg response but also insights gained from the identification of functional PAg-reactive Vγ9Vδ2 T cells and BTN3 in the alpaca and phylogenetic comparisons. Finally, we discuss models of the molecular basis of PAg recognition and implications for the development of transgenic mouse models for PAg-reactive Vγ9Vδ2 T cells. View Full-Text
Keywords: γδ T cell; phosphoantigen; BTN; butyrophilin 3; butyrophilin 2A1; evolution; alpaca; human γδ T cell; phosphoantigen; BTN; butyrophilin 3; butyrophilin 2A1; evolution; alpaca; human
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Herrmann, T.; Fichtner, A.S.; Karunakaran, M.M. An Update on the Molecular Basis of Phosphoantigen Recognition by Vγ9Vδ2 T Cells. Cells 2020, 9, 1433.

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