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The superantigen SEA binds to human γδ T cell receptor and activates γδ T cells with moderate MHC class II dependence

Uzunçayır, Sibel LU ; Petruk, Ganna LU orcid ; Mata Forsberg, Manuel ; Arasa, Claudia ; Sverremark-Ekström, Eva and Lindkvist-Petersson, Karin LU (2025) In Molecular Immunology 181. p.1-8
Abstract

Bacterial toxins, called superantigens, are produced by Staphylococcus aureus and are known to activate γδ T cells. γδ T cells contribute to long-lasting immunity against bacterial skin infections caused by S. aureus. γδ T cells are a distinct subgroup of T cells containing the T cell receptor (TCR) γ and δ chains. The γδ TCR harbouring the variable chains TRGV9/TRDV2 is the most common TCR in human peripheral blood and is known to be activated by superantigens and are also promising candidates for tumor immunotherapy. However, detailed analyses of antigen binding to γδ TCR have been severely hampered by difficulties in producing large amounts of γδ TCR. In this study, we report a protocol to produce recombinant γδ TCR (TRGV9/TRDV2) by... (More)

Bacterial toxins, called superantigens, are produced by Staphylococcus aureus and are known to activate γδ T cells. γδ T cells contribute to long-lasting immunity against bacterial skin infections caused by S. aureus. γδ T cells are a distinct subgroup of T cells containing the T cell receptor (TCR) γ and δ chains. The γδ TCR harbouring the variable chains TRGV9/TRDV2 is the most common TCR in human peripheral blood and is known to be activated by superantigens and are also promising candidates for tumor immunotherapy. However, detailed analyses of antigen binding to γδ TCR have been severely hampered by difficulties in producing large amounts of γδ TCR. In this study, we report a protocol to produce recombinant γδ TCR (TRGV9/TRDV2) by fusing the variable domains γδ TCR with the constant domains of αβ TCR. Subsequently, binding analyses were executed applying microscale thermophoresis showing a clear binding between superantigen and the γδ TCR in the micro molar range. In addition, the superantigen SEA was shown to induce cytokine expression in γδ T cells with moderate MHC dependence, suggesting that other receptors can act as antigen presenting molecules upon γδ T cell activation. These results pave the way towards a better understanding of superantigen recognition by the γδ T cells and facilitates the future use of γδ TCR in cellular tumor immunotherapy.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
SEA, Superantigen, TRGV9/TRDV2, Unconventional T cell receptor, γδ TCR
in
Molecular Immunology
volume
181
pages
8 pages
publisher
Pergamon Press Ltd.
external identifiers
  • pmid:40036925
  • scopus:85219040119
ISSN
0161-5890
DOI
10.1016/j.molimm.2025.02.019
language
English
LU publication?
yes
id
a25d7b23-554c-4659-95be-f5ec91e1cb4f
date added to LUP
2025-03-10 13:58:17
date last changed
2025-07-01 00:08:08
@article{a25d7b23-554c-4659-95be-f5ec91e1cb4f,
  abstract     = {{<p>Bacterial toxins, called superantigens, are produced by Staphylococcus aureus and are known to activate γδ T cells. γδ T cells contribute to long-lasting immunity against bacterial skin infections caused by S. aureus. γδ T cells are a distinct subgroup of T cells containing the T cell receptor (TCR) γ and δ chains. The γδ TCR harbouring the variable chains TRGV9/TRDV2 is the most common TCR in human peripheral blood and is known to be activated by superantigens and are also promising candidates for tumor immunotherapy. However, detailed analyses of antigen binding to γδ TCR have been severely hampered by difficulties in producing large amounts of γδ TCR. In this study, we report a protocol to produce recombinant γδ TCR (TRGV9/TRDV2) by fusing the variable domains γδ TCR with the constant domains of αβ TCR. Subsequently, binding analyses were executed applying microscale thermophoresis showing a clear binding between superantigen and the γδ TCR in the micro molar range. In addition, the superantigen SEA was shown to induce cytokine expression in γδ T cells with moderate MHC dependence, suggesting that other receptors can act as antigen presenting molecules upon γδ T cell activation. These results pave the way towards a better understanding of superantigen recognition by the γδ T cells and facilitates the future use of γδ TCR in cellular tumor immunotherapy.</p>}},
  author       = {{Uzunçayır, Sibel and Petruk, Ganna and Mata Forsberg, Manuel and Arasa, Claudia and Sverremark-Ekström, Eva and Lindkvist-Petersson, Karin}},
  issn         = {{0161-5890}},
  keywords     = {{SEA; Superantigen; TRGV9/TRDV2; Unconventional T cell receptor; γδ TCR}},
  language     = {{eng}},
  pages        = {{1--8}},
  publisher    = {{Pergamon Press Ltd.}},
  series       = {{Molecular Immunology}},
  title        = {{The superantigen SEA binds to human γδ T cell receptor and activates γδ T cells with moderate MHC class II dependence}},
  url          = {{http://dx.doi.org/10.1016/j.molimm.2025.02.019}},
  doi          = {{10.1016/j.molimm.2025.02.019}},
  volume       = {{181}},
  year         = {{2025}},
}