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

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Liénart, Stéphanie [UCL] Merceron, Romain Vanderaa, Christophe [UCL] Lambert, Fanny [UCL] Colau, Didier [UCL] Stockis, Julie [UCL] Coulie, Pierre G. [UCL] Lucas, Sophie [UCL]

Transforming growth factor-β1 (TGF-β1) 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 (Tregs) suppress immune cells within close proximity by activating latent TGF-β1 presented by GARP to integrin αVβ8 on their surface. We solved the crystal structure of GARP:latent TGF-β1 bound to an antibody that stabilizes the complex and blocks release of active TGF-β1. This reveals how GARP exploits an unusual medley of interactions, including fold complementation by the N terminus of TGF-β1, to chaperone and orient the cytokine for binding and activation by αVβ8. Thus, this work further elucidates the mechanism of antibody-mediated blockade of TGF-β1 activation and immunosuppression by Tregs.

Document type Article de périodique (Journal article) – Article de recherche
Publication date 2018
Language Anglais
Journal information "Science (New York, N.Y.)" - Vol. 362, no. 6417, p. 952-956 (2018)
Peer reviewed yes
e-issn 1095-9203
Publication status Publié
Affiliation UCL - SSS/DDUV/GECE - Génétique cellulaire
Links
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Bibliographic reference Liénart, Stéphanie ; Merceron, Romain ; Vanderaa, Christophe ; Lambert, Fanny ; Colau, Didier ; et. al. Structural basis of latent TGF-β1 presentation and activation by GARP on human regulatory T cells.. In: Science (New York, N.Y.), Vol. 362, no. 6417, p. 952-956 (2018)
Permanent URL http://hdl.handle.net/2078.1/204828