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Manipulation of mouse and human NK cell cytotoxicity through PVR-TIGIT interactions


Stanietsky, Noah; Lenac Roviš, Tihana; Arapović, Jurica; Babić, Marina; Levy, Ofer; Tsukerman, Pinhas; Krmpotić, Astrid; Jonjić, Stipan; Mandelboim, Ofer
Manipulation of mouse and human NK cell cytotoxicity through PVR-TIGIT interactions // 12th Meeting of the Society for Natural Immunity (NK2010), book of abstract / Jonjić, Stipan (ur.).
Rijeka, 2010. str. 60-60 (poster, međunarodna recenzija, sažetak, znanstveni)


Naslov
Manipulation of mouse and human NK cell cytotoxicity through PVR-TIGIT interactions

Autori
Stanietsky, Noah ; Lenac Roviš, Tihana ; Arapović, Jurica ; Babić, Marina ; Levy, Ofer ; Tsukerman, Pinhas ; Krmpotić, Astrid ; Jonjić, Stipan ; Mandelboim, Ofer

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

Izvornik
12th Meeting of the Society for Natural Immunity (NK2010), book of abstract / Jonjić, Stipan - Rijeka, 2010, 60-60

Skup
12th Meeting of the Society for Natural Immunity (NK2010)

Mjesto i datum
Cavtat, Hrvatska, 11-15.09.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Nk cell receptors; PVR; TIGIT; mouse cytomegalovirus

Sažetak
NK cell cytotoxicity is controlled by numerous NK inhibitory and activating receptors. Most of the inhibitory receptors bind MHC class I proteins and are expressed in a variegated fashion. We have recently shown that human TIGIT, a new protein expressed by T and NK cells binds to PVR and PVRL2 and inhibits NK cytotoxicity directly through its ITIM. Additionally, we showed that TIGIT counter inhibits the NK-mediated killing of tumor cells and protects normal cells from NK-mediated cytotoxicity thus providing an "alternative self" mechanism for MHC class I inhibition. Strikingly, PVR is also a ligand for two co-stimulating receptors, DNAM1 and CD96. Thus, it would be exciting to test what would be the in vivo functional outcome of the interactions between PVR and its various receptors. To investigate this question we have also cloned the mouse TIGIT receptors and demonstrated that the mouse TIGIT is also an inhibitory receptor as it interacts with the mouse PVR and inhibits NK cytotoxicity. Interestingly, we show that mouse cytomegalovirus could partially down regulate PVR expression, probably through the endocytosis of PVR from the cell surface. We are currently investigating the viral proteins involved in this down regulation and the functional in vivo outcome of this partial down regulation. Since TIGIT binds PVR with high affinity as compared to DNAM1 and CD96, we suggest that such partial downregulation of PVR is a fine tuning mechanism to facilitate the escape from DNAM1 and CD96 elimination, while still enabling inhibition by TIGIT.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti