Open Access
MCMV glycoprotein gp40 confers virus resistance to CD8+ T cells and NK cells in vivo
Astrid Krmpotić,Dirk H. Busch,Ivan Bubić,Friedemann Gebhardt,Hartmut Hengel,Milena Hasan,Anthony A. Scalzo,Ulrich H. Koszinowski,Stipan Jonjić +8 more
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TLDR
It is found that gp40 but not gp48 controls NK cell activation, which means that a single herpesvirus protein has a dual function in inhibiting both the adaptive as well as the innate immune response.Abstract:
The susceptibility of certain inbred mouse strains to MCMV is related to their inability to generate a strong NK cell response. We addressed here whether the MCMV susceptibility of the BALB/c strain is due to viral functions that control NK cell activation in a strains-specific manner. MCMV expresses two proteins, gp48, and gp40, that are encoded by the genes m06 and m152, respectively ; they down-regulate MHC class-I expression at the plasma membrane. Using MCMV deletion mutants and revertants we found that gp40 but nor gp48 controls NK cell activation. Absence of gp40 improved antiviral NK cell control in BALB/c but not C57BL/6 mice. Down-regulation of H60, the high affinity ligand for the NKG2D recepotr, was the mechanism by which gp40 modulates NK cell activation. Thus, a single herpesvirus protein has a dual function in inhibiting both, the adaptive as well as the innate immune response.read more
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Journal ArticleDOI
Nk cell recognition
TL;DR: The structure, function, and ligand specificity of the receptors responsible for NK cell recognition are reviewed and the role of EMT inNK cell recognition is reviewed.
Journal ArticleDOI
Roles of the NKG2D immunoreceptor and its ligands
TL;DR: This review summarizes recent findings that concern NKG2D, its ligands, its signalling properties and its role in disease, and provides a framework for considering how the induction of immune responses can be regulated by cellular responses to injury.
Journal ArticleDOI
Activation of NK cell cytotoxicity.
Mark J. Smyth,Erika Cretney,Janice M. Kelly,Jennifer A. Westwood,Shayna E. A. Street,Hideo Yagita,Kazuyoshi Takeda,Serani L.H. van Dommelen,Serani L.H. van Dommelen,Mariapia A. Degli-Esposti,Mariapia A. Degli-Esposti,Yoshihiro Hayakawa +11 more
TL;DR: The functional importance of NK cell cytotoxicity and the receptor/ligand interactions that control these processes are discussed, which are important for the pathophysiology of many diseases.
Journal ArticleDOI
Gain of Virulence Caused by Loss of a Gene in Murine Cytomegalovirus
Ivan Bubić,Markus Wagner,Astrid Krmpotić,Tanja Saulig,Sung Jin Kim,Wayne M. Yokoyama,Stipan Jonjić,Ulrich H. Koszinowski +7 more
TL;DR: To find out whether the m157 protein is the only Ly49H ligand encoded by MCMV, a m157 deletion mutant and a revertant virus were constructed and the Δm157 inhibitory phenotype was weak becauseMCMV encodes a number of proteins that mediate NK inhibition, whose contribution could be shown by another mutant.
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Regulation of immune cell function and differentiation by the NKG2D receptor.
TL;DR: Known aspects of NKG2D functions are revisited and new insights in the proposed influence of this molecule on hematopoietic differentiation are presented.
References
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Journal ArticleDOI
Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICA
Stefan Bauer,Veronika Groh,Jun Wu,Alexander Steinle,Joseph H. Phillips,Lewis L. Lanier,Thomas Spies +6 more
TL;DR: An activating immunoreceptor-MHC ligand interaction that may promote antitumor NK and T cell responses is defined.
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Selective rejection of H–2-deficient lymphoma variants suggests alternative immune defence strategy
TL;DR: It is shown that murine lymphoma cells selected for loss of H–2 expression are less malignant after low-dose inoculation in syngeneic hosts than are wild-type cells, and that the rejection of such cells is non-adaptive.
Journal ArticleDOI
ULBPs, Novel MHC Class I–Related Molecules, Bind to CMV Glycoprotein UL16 and Stimulate NK Cytotoxicity through the NKG2D Receptor
David Cosman,Jürgen Müllberg,Claire L. Sutherland,Wilson Chin,Richard J. Armitage,William C. Fanslow,Marek Kubin,N. Jan Chalupny +7 more
TL;DR: Masking of NK cell recognition of ULBP or MIC antigens by UL16 provides a potential mechanism by which human cytomegalovirus-infected cells might evade attack by the immune system.
Journal ArticleDOI
Direct Recognition of Cytomegalovirus by Activating and Inhibitory NK Cell Receptors
TL;DR: Mouse cytomegalovirus encodes an MHC-like protein that binds to an inhibitory NK cell receptor in certain MCMV-susceptible mice, and this viral protein engages a related activating receptor and confers host protection.
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An activating immunoreceptor complex formed by NKG2D and DAP10.
Jun Wu,Yaoli Song,Alexander B. H. Bakker,Stefan Bauer,Thomas Spies,Lewis L. Lanier,Joseph H. Phillips +6 more
TL;DR: In natural killer (NK) and T cells, DAP10 was identified as a cell surface adaptor protein in an activating receptor complex with NKG2D, a receptor for the stress-inducible and tumor-associated major histocompatibility complex molecule MICA.