Mouse cytomegalovirus compromises ‘missing-self’ mediated activation of natural killer cells (CROSBI ID 569119)
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Podaci o odgovornosti
Babić Čač, Marina ; Zafirova, Biljana ; Mitrović, Maja ; Pyzik, Michal ; Krmpotić, Astrid ; Vidal, Silvia M. ; Jonjić, Stipan
engleski
Mouse cytomegalovirus compromises ‘missing-self’ mediated activation of natural killer cells
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, deltam04 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.
MCMV; MHC-I; NK cells; Ly49 receptors; "missing self"
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Podaci o prilogu
3-3.
2010.
objavljeno
Podaci o matičnoj publikaciji
Podaci o skupu
Annual Meeting of the Austrian Society for Allergology and Immunology
predavanje
03.10.2010-05.10.2010
Beč, Austrija