Naslov
Mouse cytomegalovirus compromises ‘missing-self’ mediated activation of natural killer cells

Autori
Babić Čač, Marina ; Zafirova, Biljana ; Mitrović, Maja ; Pyzik, Michal ; Krmpotić, Astrid ; Vidal, Silvia M. ; Jonjić, Stipan

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

Izvornik
Annual Meeting of the Austrian Society for Allergology and Immunology, Book of Abstracts / - Beč, 2010, 3-3

Skup
Annual Meeting of the Austrian Society for Allergology and Immunology

Mjesto i datum
Beč, Austrija, 03.12.2010. - 05.12.2010

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
MCMV; MHC-I; NK cells; Ly49 receptors; "missing self"

Sažetak
Cytomegaloviruses (CMVs) are known for their ability to interfere with the immune system of their hosts. To avoid antigen presentation and recognition by CD8+ T lymphocytes, CMVs downmodulate major histocompatibility complex class I (MHC I) molecules. Yet, this process sensitizes the infected cells to ‘missing-self’ -mediated killing by NK cells. Therefore, to successfully co-evolve with their animal host CMVs had to develop strategies to avoid both CD8+ T and NK cell mediated immune responses. Murine cytomegalovirus (MCMV) encodes m152 and m06 proteins to inhibit surface expression of MHC I molecules. In addition, it encodes another protein, m04, which forms complexes with MHC I and escorts them to the cell surface. Our hypothesis is that this mechanism has evolved to prevent NK cell activation and killing by restoring the ‘self’ signature and allowing the engagement of inhibitory Ly49 receptors by their natural ligands. We here show that the cells infected with the virus lacking m04 (delta m04) were unable to activate the reporter cell line expressing inhibitory Ly49A receptor. Additionally, deltam04 MCMV was attenuated in vivo in an NK cell- and MHC I-dependent manner. Such NK cell control of the infection was dependent on the presence of NK cell subsets expressing different inhibitory Ly49 receptors. We provide evidence for immunoevasion strategy employed by CMVs aimed to avoid NK cell control via the ‘missing-self’ pathway, and present the first study emphasizing the importance of ‘missing-self’-dependent NK cell activation in the protection against viral infection in vivo.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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