Transforming growth factor–b1 (TGF-b1) 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-b1 presented by GARP (glycoprotein A repetitions predominant) to integrin aVb8 on their surface. We solved the crystal structure of GARP: latent TGF-b1 bound to an antibody that stabilizes the complex and blocks release of active TGF-b1. This Finding reveals how GARP exploits an unusual medley of interactions, including fold complementation by the amino terminus of TGF-b1, to chaperone and orient the cytokine for binding and activation by aVb8. Thus, this work further elucidates the mechanism of antibody-mediated blockade of TGF-b1 activation and immunosuppression by Tregs. [ABSTRACT FROM AUTHOR]