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

• Published in: European journal of immunology 2009-12, Vol.39 (12), p.3315-3322
• Main Authors: Stockis, Julie, Colau, Didier, Coulie, Pierre G, Lucas, Sophie
• Format: Article
• Language: English
• Subjects: Blotting, Western; CD4 Antigens - metabolism; Cell Membrane - metabolism; Cells, Cultured; Flow Cytometry; GARP; Humans; Interleukin-2 Receptor alpha Subunit - metabolism; Interleukin-7 Receptor alpha Subunit - metabolism; Jurkat Cells; Latent TGF-beta Binding Proteins - genetics; Latent TGF-beta Binding Proteins - metabolism; Lymphocyte Activation - immunology; Membrane Proteins - genetics; Membrane Proteins - metabolism; Models, Biological; Muromonab-CD3 - immunology; Protein Binding; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; TGF‐b; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Treg
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200939684

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.