Manuela Fiedler

Identification of cellular ligands for
CMV-encoded Fcgamma receptors

Cellular IgG-binding Fc-gamma receptors are expressed on immune cells like natural killer (NK) cells and monocytes. Interestingly, members of the alpha- and beta-herpesviridae do also express Fc-gamma receptors (vFcgammaRs) on the surface of infected cells and on the virion surface that bind to the constant Fc-part of IgG. For the mouse CMV the Fc-gamma receptor is encoded by the gene fcr-1/m138 (Thäle R. et al.,1994), the human CMV-vFcRs are encoded by IRL/TRL11/gp34 and UL119-118/gp68 (Atalay, R. & Zimmermann A. et al., 2002). According to the model of “antibody bipolar bridging”, vFcgammaRs are thought to protect the infected cell by binding to the Fc-part of immune IgG and thus inhibiting the activation of host FcgammaRs.
Isolated expression of MCMV fcr-1 and experiments with the deletion mutant delta-m138/fcr-1 of MCMV revealed also IgG-independent function of fcr-1 (Lenac T. & Budt M. et al., 2006). Fcr-1/m138 was efficient in downregulating MULT-1 and H60 which are ligands of the activating NKG2D receptor, thus identifying fcr-1 as an antagonist of the NK-cell response.
Aim of the study is to identify binding partners of the HCMV-encoded Fc-gammaRs. Therefor soluble epitope tagged FcgammaRs-mutants were constructed. Potential binding partners will be identified after incubation with human immune cells by FACS detection.

1st supervisor: Prof. Dr. Hartmut Hengel
2nd supervisor:               

Institute:
Department of Virology, Heinrich Heine University Düsseldorf

Telephone: +49 (0)211 - 81 - 10552
E-mail: manuela.fiedler@uni-duesseldorf.de