An Update on the Molecular Basis of Phosphoantigen Recognition by Vγ9Vδ2 T Cells
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 (<i>TRGV9JP</i> or Vγ2Jγ1.2) and are paired with Vδ2 (<i>TRDV2</i>)-containing δ-chains. These TCRs r...
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MDPI AG
2020-06-01
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| author | Thomas Herrmann Alina Suzann Fichtner Mohindar Murugesh Karunakaran |
| author_facet | Thomas Herrmann Alina Suzann Fichtner Mohindar Murugesh Karunakaran |
| author_sort | Thomas Herrmann |
| collection | DOAJ |
| description | 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 (<i>TRGV9JP</i> or Vγ2Jγ1.2) and are paired with Vδ2 (<i>TRDV2</i>)-containing δ-chains. These TCRs respond to phosphoantigens (PAg) such as (<i>E</i>)-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. |
| first_indexed | 2024-03-10T19:15:49Z |
| format | Article |
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| language | English |
| last_indexed | 2024-03-10T19:15:49Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj.art-36115de452a74198bd15bd15564961992023-11-20T03:21:05ZengMDPI AGCells2073-44092020-06-0196143310.3390/cells9061433An Update on the Molecular Basis of Phosphoantigen Recognition by Vγ9Vδ2 T CellsThomas Herrmann0Alina Suzann Fichtner1Mohindar Murugesh Karunakaran2Institute for Virology and Immunobiology, Department of Medicine, University of Wuerzburg, 97070 Wuerzburg, GermanyInstitute of Immunology, Hannover Medical School, 30559 Hannover, GermanyInstitute for Virology and Immunobiology, Department of Medicine, University of Wuerzburg, 97070 Wuerzburg, GermanyAbout 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 (<i>TRGV9JP</i> or Vγ2Jγ1.2) and are paired with Vδ2 (<i>TRDV2</i>)-containing δ-chains. These TCRs respond to phosphoantigens (PAg) such as (<i>E</i>)-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.https://www.mdpi.com/2073-4409/9/6/1433γδ T cellphosphoantigenBTNbutyrophilin 3butyrophilin 2A1evolution |
| spellingShingle | Thomas Herrmann Alina Suzann Fichtner Mohindar Murugesh Karunakaran An Update on the Molecular Basis of Phosphoantigen Recognition by Vγ9Vδ2 T Cells Cells γδ T cell phosphoantigen BTN butyrophilin 3 butyrophilin 2A1 evolution |
| title | An Update on the Molecular Basis of Phosphoantigen Recognition by Vγ9Vδ2 T Cells |
| title_full | An Update on the Molecular Basis of Phosphoantigen Recognition by Vγ9Vδ2 T Cells |
| title_fullStr | An Update on the Molecular Basis of Phosphoantigen Recognition by Vγ9Vδ2 T Cells |
| title_full_unstemmed | An Update on the Molecular Basis of Phosphoantigen Recognition by Vγ9Vδ2 T Cells |
| title_short | An Update on the Molecular Basis of Phosphoantigen Recognition by Vγ9Vδ2 T Cells |
| title_sort | update on the molecular basis of phosphoantigen recognition by vγ9vδ2 t cells |
| topic | γδ T cell phosphoantigen BTN butyrophilin 3 butyrophilin 2A1 evolution |
| url | https://www.mdpi.com/2073-4409/9/6/1433 |
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