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NK cell recognition of the ‘missing-self’ is relevant in the recognition and control of a viral pathogen in vivo


Babić, Marina; Zafirova, Biljana; Mitrović, Maja; Pyzik, Michal; Krmpotić, Astrid; Vidal, Silvia M.; Jonjić, Stipan
NK cell recognition of the ‘missing-self’ is relevant in the recognition and control of a viral pathogen in vivo // Natural Killer Cell Symposium NK2011
Mainz, 2011. (predavanje, međunarodna recenzija, sažetak, znanstveni)


Naslov
NK cell recognition of the ‘missing-self’ is relevant in the recognition and control of a viral pathogen in vivo

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

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

Izvornik
Natural Killer Cell Symposium NK2011 / - Mainz, 2011

Skup
Natural Killer Cell Symposium NK2011

Mjesto i datum
Mainz, Njemačka, 18-20.04.2011

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
MCMV; NK stanice; Ly49 receptori; missing self
(MCMV; NK cells; Ly49 receptors; missing self)

Sažetak
In order to sidestep antigen presentation and recognition by CD8+T cells, cytomegaloviruses (CMVs) encode immunoevasion proteins that downmodulate the expression of MHC class I on the surface of infected cells. However, by lowering interactions and triggering through inhibitory Ly49 receptors, this process makes infected cells prone to ‘missing-self’ -mediated killing by NK cells. The aim of this study was to explain the mechanisms by which MCMV avoids NK cell control, in spite of the early and strong downregulation of MHC-I molecules on the surface of infected cells. MCMV encodes three proteins involved in the regulation of MHC-I expression. The m152-encoded gp40 glycoprotein arrests MHC-I at the level of the ERGIC/cis-Golgi compartment, whereas m06-encoded gp48 redirects MHC-I complexes to lysosomes for degradation. The third MCMV regulator of MHC-I expression is gp34, encoded by the m04 gene. Unlike the other two, m04/gp34 does not prevent the surface expression of MHC-I but instead binds to these proteins in the ER, forming complexes that can reach the cell surface. It has been suggested that m04/gp34 might inhibit NK cell activation through its ability to escort MHC-I to the cell surface and serve as an NK cell decoy. Our hypothesis was that this mechanism 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. In addition, we have evidence that m04/gp34 is essential for the recognition of infected cells by the activating Ly49P and Ly49L receptors, which both recognize MHC-I molecule (H-2Dk or H-2Dd, respectively), together with m04 product and another, so far unidentified viral component. Here we show that the target cells infected with the virus lacking m04 (m04) were unable to activate a reporter cell line expressing inhibitory Ly49A receptor. Additionally, 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. Therefore, here we provide the first evidence that NK cell recognition of the ‘missing-self’ is relevant in the recognition and control of a viral pathogen in vivo. However, our preliminary data show that in addition, also other MCMV encoded MHC-I-like molecules might serve to engage inhibitory Ly49 receptors and it remains to be determined how these contribute to compromise ‘missing-self’ mediated recognition of infected cells.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
062-0621261-1263 - Molekularni mehanizmi citomegalovirusnog izmicanja imunološkom nadzoru (Stipan Jonjić, )
062-0621261-1268 - Uloga imunosubverzivnih citomegalovirusnih gena u latenciji (Astrid Krmpotić, )

Ustanove
Medicinski fakultet, Rijeka

Citiraj ovu publikaciju

Babić, Marina; Zafirova, Biljana; Mitrović, Maja; Pyzik, Michal; Krmpotić, Astrid; Vidal, Silvia M.; Jonjić, Stipan
NK cell recognition of the ‘missing-self’ is relevant in the recognition and control of a viral pathogen in vivo // Natural Killer Cell Symposium NK2011
Mainz, 2011. (predavanje, međunarodna recenzija, sažetak, znanstveni)
Babić, M., Zafirova, B., Mitrović, M., Pyzik, M., Krmpotić, A., Vidal, S. & Jonjić, S. (2011) NK cell recognition of the ‘missing-self’ is relevant in the recognition and control of a viral pathogen in vivo. U: Natural Killer Cell Symposium NK2011.
@article{article, year = {2011}, keywords = {MCMV, NK cells, Ly49 receptors, missing self}, title = {NK cell recognition of the ‘missing-self’ is relevant in the recognition and control of a viral pathogen in vivo}, keyword = {MCMV, NK cells, Ly49 receptors, missing self}, publisherplace = {Mainz, Njema\v{c}ka} }