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Cited by 69T-cell and B-cell ImmunologyImmunotherapy and Immune ResponsesImmune Cell Function and Interaction

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

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Herrmann, Thomas, Fichtner, Alina Suzann, Karunakaran, Mohindar Murugesh·2020·Cells
DOI 10.3390/cells9061433PMC PMC7348870
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Abstract

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.

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  • Vγ9Vδ2+ T cells remain responsive to both pyrophosphate antigens (pAg) and anti-CD3 stimulation.

    “Notably, Vγ9Vδ2+ T cells remain responsive to both pyrophosphate antigens (pAg) and anti-CD3 stimulation, a feature that underlies their potential use in several cancer immunotherapy applications (24), and they also exhibit the potential for further TCR-mediated plasticity (25).”

    From Comparing Mouse and Human Tissue-Resident γδ T Cells (2022) · cites this paper as [24]

    Section 2.3 states that Vγ9Vδ2 T cells respond to phosphoantigens. Section 3.1 reports anti-CD3-triggered IL-2 production, but in murine reporter cells transduced with a Vγ9Vδ2 TCR, not in Vγ9Vδ2 T cells themselves. The paper therefore supports the phosphoantigen response but not the anti-CD3 claim at the population level stated. Page numbers are unavailable in our copy. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Herrmann, T., Fichtner, A. S., & Karunakaran, M. M.
Affiliations
  • University of Würzburg (DE)
  • Medizinische Hochschule Hannover (DE)
Corresponding author
Herrmann, Thomas
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2020-06-09
Volume
9
Issue
6
Pages
1433
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells9061433
PMC
PMC7348870
OpenAlex
W3034818843
Cited by
69
References
0
Citations by year
2026: 10 · 2025: 8 · 2024: 8 · 2023: 8 · 2022: 12 · 2021: 15 · 2020: 8
FWCI
1.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Online Publication Service of Würzburg University (Würzburg University) (submittedVersion, cc-by)
Funders
  • Deutsche Forschungsgemeinschaft (DFG-He 2346-7/1, DFG-He 2346-8/1, DFG-RA 3077/1-1)
  • Wilhelm Sander-Stiftung (2013.907.2)
  • Deutsche Krebshilfe (70000?)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
Keywords
Vγ9Vδ2 T cells, HMBPP, isopentenyl pyrophosphate, BTN2A1, T cell receptor delta chain, alpaca, transgenic mouse model, aminobisphosphonates, zoledronic acid, phylogenetic comparison
MeSH terms
Animals, Humans, T-Lymphocytes, Antigens, CD

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