Naslov
THE MCMV M04 PROTEIN PLAYS A KEY ROLE IN NK CELL INHIBITION 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
European journal of immunology / Livingstone Cate - Weinheim : Wiley-VCH, 2009, S626-S626

Skup
European Congress of Immunology (ECI)

Mjesto i datum
Berlin, Njemačka, 13.09.2009. - 16.09.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
MCMV; Ly49; NK cells

Sažetak
The ability of herpesviruses to regulate NK cells is perhaps best illustrated in mice infected with mousecytomegalovirus (MCMV). Like many other viruses, MCMVdownregulates MHC class I molecules in order to compromise the CD8 T cell response. Since this function should sensitize theinfected cells to NK cells via missing self-dependentmechanisms, the virus had to deal with this threat. Unlike twoother 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 toinhibitory NK cell receptors. We have now evidence that thevirus lacking m04 is attenuated in NK cell- and MHC I-dependent manner in several mouse strains. Furthermore, byusing the reporter cell assay, we have evidence that 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 otherinhibitors of MHC class I molecules. Interestingly, some mouse strains possess the activating Ly49 receptor specific for MHCclass I expressed in complex with m04. We have recently shownthat the Ly49P recognition of MCMV-infected cells expressing H2-Dk and m04 is associated with NK cell-mediated resistancein the MA/My mouse (Kielczewska A, Pyzik M, Sun T, Krmpotic A, Lodoen MB, Munks MW, Babic M, Hill AB, Koszinowski UH, Jonjic, Lanier LL, Vidal SM, J Exp Med in press).

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA