Naslov
THE MCMV M04 PROTEIN PLAYS A KEY ROLE IN PREVENTION OF NK CELL ACTIVATION VIA „MISSING SELF“ MECHANISM

Autori
Babic, Marina ; Pyzik, Michal ; Kielczewska, Agnieszka ; Krmpotic, Astrid ; Vidal, Silvia M. ; Jonjic, Stipan

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

Izvornik
2009 Annual Meeting of the Croatian Immunological Society ; Book of abstracts / Rabatić , Sabina - Zagreb : Hrvatsko prirodoslovno društvo, 2009

Skup
2009 Annual Meeting of the Croatian Immunological Society

Mjesto i datum
Starigrad, Hrvatska, 01.10.2009. - 04.10.2009

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
MCMV; Ly49; NK stanice
(MCMV; Ly49; NK cells)

Sažetak
Mice infected with mouse cytomegalovirus (MCMV) present a valuable model to study the ability of herpesviruses to regulate NK cells. Like many other viruses, MCMV downregulates MHC class I molecules in order to compromise the CD8+ T cell response. Yet, the lack of MHC class I molecules should sensitize the infected cells to recognition by NK cells via „missing self“-dependent mechanisms. To avoid this, the virus had to invent additional evasion mechanism. It has been proposed (Kleijnen et al., EMBO J, 1997) that the function of MCMV m04 protein is to inhibit NK cells by rescuing surface expression of class I proteins to serve as ligands to inhibitory NK cell receptors. Of note is that m04 binds to MHC class I molecules, forming complexes that reach the cell surface. We showed that the virus lacking m04 is attenuated in NK cell- and MHC class I- dependent manner in several mouse strains. Furthermore, by using the reporter cell assay, we provided evidence that the presence of m04 can rescue the engagement of inhibitory Ly49A receptor, as compared to the situation when the cells are infected with the virus lacking m04, but possessing two other inhibitors of MHC class I molecules. Interestingly, we have recently shown that the recognition of MCMV-infected cells expressing H2-Dk and m04 via activating Ly49P receptor is associated with NK cell-mediated resistance in the MA/My mice (Kielczewska et al., J Exp Med, 2009). This indicates that the co-evolution of the virus with its host resulted in numerous specific mechanisms that sequentially evolved in attempts to outsmart each other and survive.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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