Naslov
The herpesviral Fc receptor fcr-1 down-regulates the NKG2D ligands MULT-1 and H60

Autori
Lenac, Tihana ; Budt, Matthias ; Arapović, Jurica ; Hasan, Milena ; Zimmermann, Albert ; Šimić, Hrvoje ; Krmpotić, Astrid ; Messerle, Martin ; Ruzsics, Zsolt ; Koszinowski, Ulrich H ; Hengel, Hartmut ; Jonjić, Stipan

Izvornik
Journal of Experimental Medicine (0022-1007) 203 (2006), 8; 1843-1850

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
fcr-1; NKG2D; MULT-1; H60

Sažetak
Members of the a- and b-subfamily of herpesviridae encode glycoproteins that specifi cally bind to the Fc part of immunoglobulin (Ig)G. Plasma membrane resident herpesviral Fc receptors seem to prevent virus-specifi c IgG from activating antibody-dependent effector functions. We show that the mouse cytomegalovirus (MCMV) molecule fcr-1 promotes a rapid down-regulation of NKG2D ligands murine UL16-binding protein like transcript (MULT)-1 and H60 from the cell surface. Deletion of the m138/ fcr-1 gene from the MCMV genome attenuates viral replication to natural killer (NK) cell response in an NKG2Ddependent manner in vivo. A distinct N-terminal module within the fcr-1 ectodomain in conjunction with the fcr-1 transmembrane domain was required to dispose MULT-1 to degradation in lysosomes. In contrast, down-modulation of H60 required the complete fcr-1 ectodomain, implying independent modes of fcr-1 interaction with the NKG2D ligands. The results establish a novel viral strategy for down-modulating NK cell responses and highlight the impressive diversity of Fc receptor functions.

Izvorni jezik
Engleski

POVEZANOST RADA