Viral modulation of CD1 antigen presentation

• Applicant: Professor Dr. Günther Schönrich
• Subject Area: Virology
• Term: from 2009 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 105246303

During viral infections the immune system detects peptide epitopes associated with polymorphic major histocompatibility complex (MHC) molecules as well as lipid antigens bound to nonpolymorphic CD1 molecules. CD1-restricted T cells include lymphocytes which express markers of the NK cell lineage and an invariant T cell receptor that recognises CD1d ligands. These natural killer T(NKT) cells bridge the innate and adaptive immune system. In previous work we could demonstrate virus-associated mechanisms that activate NKT cells. We observed a novel “missing self” mechanism: cells counterbalance the virus-induced loss of MHC class I proteins by increasing transport of CD1d proteins to the surface. The NKT cell activation resulting thereof enhances the antiviral defence. On the other side, we have also shown that herpesviruses have evolved countermeasures that interfere with antigen presentation through CD1 molecules. We could identify three novel herpesviral molecules that specifically target CD1 expression on infected cells. In this grant proposal we will further clarify the molecular details that lead to activation of NKT cells in the course of virus infection and the function of NKT cell subsets in the antiviral immune defence. Finally, we will elucidate the precise mechanisms by which the newly identified herpesviral immune evasion proteins block CD1 antigen presentation. The anticipated results will not only help to understand viral pathogenesis but will also elucidate the physiology of CD1 antigen presentation leading to novel strategies of antiviral intervention.

• DFG Programme: Research Grants