Naslov
The herpesviral Fc eceptor fcr-1 as a potent Down-regulator of the NKG2D ligand 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

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstracts of the 1st Joint Meeting of European National Societies of Immunology ang the 16th European Congress of Immunology / - , 2006

Skup
Meeting of European National Societies of Immunology (1 ; 2006) ; European Congress of Immunology (16 ; 2005)

Mjesto i datum
Pariz, Francuska, 06.09.2006. - 09.09.2006

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

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

Sažetak
Members of the alpha- and beta- subfamily of herpesviridae encode glycoproteins that specifically bind to the Fc part of IgG. Plasma membrane resident herpesviral Fc receptors seem to prevent virus-specific IgG from activating antibody dependent effector functions. We show that the mouse cytomegalovirus (MCMV) molecule fcr-1 is able to down-regulate NKG2D ligands MULT-1 and H60. fcr-1 promotes rapid down-regulation of MULT-1 from the surface of infected cells to a lysosomal compartment for proteolytic degradation via clathrin-dependent endocytosis. Removal of MULT-1 from the plasma membrane by fcr-1 occured independent of, but in cooperation with the second MCMV inhibitor of MULT-1, m145. Deletion of the fcr-1/m138 gene from the MCMV genome attenuated viral replication to NK cell responses in vivo. A distinct N’ terminal module within the fcr-1 ectodomain was necessary and sufficient to impair MULT-1 surface expression. 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