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Structural basis of latent TGF-β1 presentation and activation by GARP on human regulatory T cells

(2018) SCIENCE. 362(6417). p.952-956
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Abstract
Transforming growth factor-beta 1 (TGF-beta 1) is one of very few cytokines produced in a latent form, requiring activation to exert any of its vastly diverse effects on development, immunity, and cancer. Regulatory T cells (T-regs) suppress immune cells within close proximity by activating latent TGF-beta 1 presented by GARP (glycoprotein A repetitions predominant) to integrin alpha V beta 8 on their surface. We solved the crystal structure of GARP: latent TGF-beta 1 bound to an antibody that stabilizes the complex and blocks release of active TGF-beta 1. This finding reveals how GARP exploits an unusual medley of interactions, including fold complementation by the amino terminus of TGF-beta 1, to chaperone and orient the cytokine for binding and activation by alpha V beta 8. Thus, this work further elucidates the mechanism of antibody-mediated blockade of TGF-beta 1 activation and immunosuppression by T-regs.
Keywords
TGF-BETA, PROTEINS, SURFACE

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Chicago
Lienart, Stephanie, Romain Merceron, Christophe Vanderaa, Fanny Lambert, Didier Colau, Julie Stockis, Bas van der Woning, et al. 2018. “Structural Basis of Latent TGF-β1 Presentation and Activation by GARP on Human Regulatory T Cells.” Science 362 (6417): 952–956.
APA
Lienart, S., Merceron, R., Vanderaa, C., Lambert, F., Colau, D., Stockis, J., van der Woning, B., et al. (2018). Structural basis of latent TGF-β1 presentation and activation by GARP on human regulatory T cells. SCIENCE, 362(6417), 952–956.
Vancouver
1.
Lienart S, Merceron R, Vanderaa C, Lambert F, Colau D, Stockis J, et al. Structural basis of latent TGF-β1 presentation and activation by GARP on human regulatory T cells. SCIENCE. 2018;362(6417):952–6.
MLA
Lienart, Stephanie et al. “Structural Basis of Latent TGF-β1 Presentation and Activation by GARP on Human Regulatory T Cells.” SCIENCE 362.6417 (2018): 952–956. Print.
@article{8586563,
  abstract     = {Transforming growth factor-beta 1 (TGF-beta 1) is one of very few cytokines produced in a latent form, requiring activation to exert any of its vastly diverse effects on development, immunity, and cancer. Regulatory T cells (T-regs) suppress immune cells within close proximity by activating latent TGF-beta 1 presented by GARP (glycoprotein A repetitions predominant) to integrin alpha V beta 8 on their surface. We solved the crystal structure of GARP: latent TGF-beta 1 bound to an antibody that stabilizes the complex and blocks release of active TGF-beta 1. This finding reveals how GARP exploits an unusual medley of interactions, including fold complementation by the amino terminus of TGF-beta 1, to chaperone and orient the cytokine for binding and activation by alpha V beta 8. Thus, this work further elucidates the mechanism of antibody-mediated blockade of TGF-beta 1 activation and immunosuppression by T-regs.},
  author       = {Lienart, Stephanie and Merceron, Romain and Vanderaa, Christophe and Lambert, Fanny and Colau, Didier and Stockis, Julie and van der Woning, Bas and De Haard, Hans and Saunders, Michael and Coulie, Pierre G and Savvides, Savvas and Lucas, Sophie},
  issn         = {0036-8075},
  journal      = {SCIENCE},
  keywords     = {TGF-BETA,PROTEINS,SURFACE},
  language     = {eng},
  number       = {6417},
  pages        = {952--956},
  title        = {Structural basis of latent TGF-β1 presentation and activation by GARP on human regulatory T cells},
  url          = {http://dx.doi.org/10.1126/science.aau2909},
  volume       = {362},
  year         = {2018},
}

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