Naslov
The MCMV m04 protein plays a key role in prevention of NK cell activation via a "missing self" mechanism

Autori
Babić, Marina ; Pyzik, M ; Krmpotić, Astrid ; Vidal, S.M. ; Jonjić, Stipan

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

Izvornik
12th International CMV/BetaHerpesvirus Workshop May 10-14, 2009 Boston, Massachusettes / Kowalik, T ; Compton, T. - Boston (MA), 2009, 3.01-3.01

Skup
12th International CMV/BetaHerpesvirus Workshop May 10-14, 2009 Boston, Massachusettes

Mjesto i datum
Boston (MA), Sjedinjene Američke Države, 10.05.2009. - 14.05.2009

Vrsta sudjelovanja
Plenarno

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
MCMV; m04; NK

Sažetak
The ability of herpesviruses to regulate NK cells is perhaps best illustrated in mice infected with mouse cytomegalovirus (MCMV). Like many other viruses, MCMV downregulates MHC class I molecules in order to compromise the CD8 T cell response. Since this function should sensitize the infected cells to NK cells via "missing self"-dependent mechanisms, the virus had to deal with this threat. Unlike two other MCMV regulators of MHC class I molecules (m06, m152), the m04 does not prevent MHC class I expression, but in contrast, it binds to MHC class I, forming complexes that reach the cell surface (Kleijnen et al., EMBO J, 1997.). Based on this, it has been proposed that this function of m04 may serve the virus to inhibit NK cells by providing ligands to inhibitory NK cell receptors. We have now evidence 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 have evidence that the presence of m04 can rescue the engagement of inhibitory Ly49 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, some mouse strains possess the activating Ly49 receptor specific for MHC class I expressed in complex with m04. We have recently shown that the Ly49P recognition of MCMV-infected cells expressing H2-Dk and m04 is associated with NK cell-mediated resistance in the MA/My mouse

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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