Molecular and functional analyses of CD25 as a target for ADP-ribosylation on CD4+/CD25+ regulatory T cells

• Applicant: Professor Dr. Friedrich Koch-Nolte
• Subject Area: Immunology
• Term: from 2006 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 32541694

NAD-dependent ADP-ribosylation is one of the posttranslational protein modifications, best known as the pathogenic mechanism of bacterial toxins. ART2 is a toxin-related argininespecific ADP-ribosyltransferase that is expressed by murine T cells as an ecto-enzyme in association with lipid rafts. Inflammation leads to the release of the ART2 substrate NAD from damaged cells. ART2 then catalyzes ADP-ribosylation of raft-associated signalling proteins. ART2 is shed from the T cell surface as an active enzyme upon T cell activation. Shed ART2 ADP-ribosylates secretory proteins including certain cytokines. ADP-riboslyation of membrane and secretory proteins can profoundly influence the function, intercellular communication, and interaction of inflammatory cells. We recently discovered that CD25, the alpha chain of the interleukin-2 receptor, which is constirutively expressed by regulatroy T cells, is a prominent target for ADP-ribosylation. The goal of the proposed project is to identify the arginine residue in CD25 that serves as the acceptor for ADP-ribosylation and to determine the consequences of this modification for the function of CD25. Moreover we will evaluate the effects of CD25-ADP-ribosylation on the function of regulatory T cells.

• DFG Programme: Research Grants
• International Connection: France
• Participating Persons: Professor Dr. Olivier Boyer; Professor Dr. Michel Seman