Membrane protein GARP is a receptor for latent TGF-β on the surface of activated human Treg

Abstract

Human Treg and Th clones secrete the latent form of TGF-β, in which the mature TGF-β protein is bound to the latency-associated peptide (LAP), and is thereby prevented from binding to the TGF-β receptor. We previously showed that upon TCR stimulation, human Treg clones but not Th clones produce active TGF-β and bear LAP on their surface. Here, we show that latent TGF-β, i.e. both LAP and mature TGF-β, binds to glycoprotein A repetitions predominant (GARP), a transmembrane protein containing leucine rich repeats, which is present on the surface of stimulated Treg clones but not on Th clones. Membrane localization of latent TGF-β mediated by binding to GARP may be necessary for the ability of Treg to activate TGF-β upon TCR stimulation. However, it is not sufficient as lentiviral-mediated expression of GARP in human Th cells induces binding of latent TGF-β to the cell surface, but does not result in the production of active TGF-β upon stimulation of these Th cells. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.