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

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 31st Annual Workshop IHW 2006 / - , 2006

Skup
IHW Annual Workshop (31 ; 2006)

Mjesto i datum
Seattle (WA), Sjedinjene Američke Države, 22.07.2006. - 28.07.2006

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
fcr-1; NKG2D

Sažetak
NKG2D is a dominant activating NK cell receptor involved in immune responses to viruses. We have recently identified three mouse cytomegalovirus (MCMV) proteins which selectively target NKG2D ligands for attenuating NK cell response during the infection. The m152-encoded gp40 serves as a modulator of the RAE-1 family of NKG2D ligands, the product of MCMV m155 gene down-modulates H60, whereas the m145-encoded protein affects the expression of MULT-1. However, the deletion of m145 or m155 gene from the MCMV genome could not fully explain MULT-1 and H60 down-regulation. This prompted us to continue in vitro screen for additional inhibitors using MCMV mutants lacking different sets of non-essential genes. Our latest data established that the MCMV receptor for the Fc fragment of IgG, encoded by m138/fcr-1 gene, selectively down-modulates the expression of NKG2D ligands MULT-1 and H60 on the surface of infected cells. Herpesviruses are known to encode transmembrane glycoproteins serving as viral Fc receptors and fcr-1 is the only such protein determined for the MCMV. We have previously found that MCMV lacking m138/fcr-1 is severely attenuated in vivo during the primary phase of infection in which IgG does not contribute to the immune control. Here we demonstrated that fcr-1 enhances MCMV replication in vivo in the NKG2D- and NK cell- dependent manner and thus provided the explanation for the attenuation of m138/fcr-1 deletion mutant in IgG-deficient mice. We showed that fcr-1 interferes with the recycling of surface MULT-1 and leads to its subsequent degradation in lysosomes. A distinct N’ terminal module within the fcr-1 ectodomain was necessary and sufficient to impair MULT-1 surface expression. In contrast, the down-modulation of H60 required the complete fcr-1 ectodomain, implying independent modes of fcr-1 interaction with the NKG2D ligands.

Izvorni jezik
Engleski

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