scholarly journals Modulation of Natural Killer Cell Cytotoxicity in Human Cytomegalovirus Infection: The Role of Endogenous Class I Major Histocompatibility Complex and a Viral Class I Homolog

1998 ◽  
Vol 187 (10) ◽  
pp. 1681-1687 ◽  
Author(s):  
Clement C. Leong ◽  
Tara L. Chapman ◽  
Pamela J. Bjorkman ◽  
Danuska Formankova ◽  
Edward S. Mocarski ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Class I ◽  
Inhibitory Receptors ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Infected Cells

Natural killer (NK) cells have been implicated in early immune responses against certain viruses, including cytomegalovirus (CMV). CMV causes downregulation of class I major histocompatibility complex (MHC) expression in infected cells; however, it has been proposed that a class I MHC homolog encoded by CMV, UL18, may act as a surrogate ligand to prevent NK cell lysis of CMV-infected cells. In this study, we examined the role of UL18 in NK cell recognition and lysis using fibroblasts infected with either wild-type or UL18 knockout CMV virus, and by using cell lines transfected with the UL18 gene. In both systems, the expression of UL18 resulted in the enhanced killing of target cells. We also show that the enhanced killing is due to both UL18-dependent and -independent mechanisms, and that the killer cell inhibitory receptors (KIRs) and CD94/NKG2A inhibitory receptors for MHC class I do not play a role in affecting susceptibility of CMV-infected fibroblasts to NK cell–mediated cytotoxicity.

scholarly journals The Murine Nonclassical Class I Major Histocompatibility Complex–like CD1.1 Molecule Protects Target Cells from Lymphokine-activated Killer Cell Cytolysis

1999 ◽  
Vol 189 (3) ◽  
pp. 483-491 ◽  
Author(s):  
Chew Shun Chang ◽  
Laurent Brossay ◽  
Mitchell Kronenberg ◽  
Kevin P. Kane
Keyword(s):  
Major Histocompatibility Complex ◽  
Nk Cell ◽  
Killer Cell ◽  
Class I ◽  
Target Cells ◽  
Inhibitory Receptor ◽  
Major Histocompatibility ◽  
Lymphokine Activated Killer Cell ◽  
Histocompatibility Complex ◽  
Nonclassical Class

Classical class I major histocompatibility complex (MHC) molecules, as well as the nonclassical class I histocompatibility leukocyte antigen (HLA)-E molecule, can negatively regulate natural killer (NK) cell cytotoxicity through engagement of NK inhibitory receptors. We show that expression of murine (m)CD1.1, a nonpolymorphic nonclassical MHC class I–like molecule encoded outside the MHC, protects NK-sensitive RMA/S target cells from adherent lymphokine-activated killer cell (A-LAK) cytotoxicity. Passage of effector cells in recombinant interleukin (rIL)-2 enhanced protection by mCD1.1, suggesting an expansion of relevant A-LAK population(s) or modulation of A-LAK receptor expression. Murine CD1.1 conferred protection from lysis by rIL-2–activated spleen cells of recombination activating gene (Rag)-1−/− mice, which lack B and T cells, demonstrating that mCD1.1 can protect RMA/S cells from lysis by NK cells. An antibody specific for mCD1.1 partially restored A-LAK lysis of RMA/S.CD1.1 transfectants, indicating that cell surface mCD1.1 can confer protection from lysis; therefore, mCD1.1 possibly acts through interaction with an NK inhibitory receptor. CD1.1 is by far the most divergent class I molecule capable of regulating NK cell activity. Finally, mCD1.1 expression rendered RMA/S cells resistant to lysis by A-LAK of multiple mouse strains. The conserved structure of mCD1.1 and pattern of mCD1.1 resistance from A-LAK lysis suggest that mCD1.1 may be a ligand for a conserved NK inhibitory receptor.

scholarly journals Influenza Virus Infection Augments NK Cell Inhibition through Reorganization of Major Histocompatibility Complex Class I Proteins

2008 ◽  
Vol 82 (16) ◽  
pp. 8030-8037 ◽  
Author(s):  
Hagit Achdout ◽  
Irit Manaster ◽  
Ofer Mandelboim
Keyword(s):  
Influenza Virus ◽  
Major Histocompatibility Complex ◽  
Virus Infection ◽  
Mhc Class I ◽  
Nk Cell ◽  
Influenza Virus Infection ◽  
Class I ◽  
Inhibitory Receptors ◽  
Histocompatibility Complex ◽  
Infected Cells

ABSTRACT The killing by natural killer (NK) cells is regulated by inhibitory, costimulatory, and activating receptors. The inhibitory receptors recognize mainly major histocompatibility complex (MHC) class I molecules, while the activating NK receptors recognize stress-induced ligands and viral products. Thus, changes in the expression of the various inhibitory and activating ligands will determine whether target cells will be killed or protected. Here, we demonstrate that after influenza virus infection the binding of the two NK inhibitory receptors, KIR2DL1 and the LIR1, to the infected cells is specifically increased. The increased binding occurs shortly after the influenza virus infection, prior to the increased recognition of the infected cells by the NK activating receptor, NKp46. We also elucidate the mechanism responsible for this effect and demonstrate that, after influenza virus infection, MHC class I proteins redistribute on the cell surface and accumulate in the lipid raft microdomains. Such redistribution allows better recognition by the NK inhibitory receptors and consequently increases resistance to NK cell attack. In contrast, T-cell activity was not influenced by the redistribution of MHC class I proteins. Thus, we present here a novel mechanism, developed by the influenza virus, of inhibition of NK cell cytotoxicity, through the reorganization of MHC class I proteins on the cell surface.

scholarly journals Mouse CD94/NKG2A Is a Natural Killer Cell Receptor for the Nonclassical Major Histocompatibility Complex (MHC) Class I Molecule Qa-1b

1998 ◽  
Vol 188 (10) ◽  
pp. 1841-1848 ◽  
Author(s):  
Russell E. Vance ◽  
Jennifer R. Kraft ◽  
John D. Altman ◽  
Peter E. Jensen ◽  
David H. Raulet
Keyword(s):  
Major Histocompatibility Complex ◽  
Nk Cells ◽  
Natural Killer ◽  
Mhc Class I ◽  
Killer Cell ◽  
Class I ◽  
Target Cells ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecule

Natural killer (NK) cells preferentially lyse targets that express reduced levels of major histocompatibility complex (MHC) class I proteins. To date, the only known mouse NK receptors for MHC class I belong to the Ly49 family of C-type lectin homodimers. Here, we report the cloning of mouse NKG2A, and demonstrate it forms an additional and distinct class I receptor, a CD94/NKG2A heterodimer. Using soluble tetramers of the nonclassical class I molecule Qa-1b, we provide direct evidence that CD94/NKG2A recognizes Qa-1b. We further demonstrate that NK recognition of Qa-1b results in the inhibition of target cell lysis. Inhibition appears to depend on the presence of Qdm, a Qa-1b-binding peptide derived from the signal sequences of some classical class I molecules. Mouse NKG2A maps adjacent to CD94 in the heart of the NK complex on mouse chromosome six, one of a small cluster of NKG2-like genes. Our findings suggest that mouse NK cells, like their human counterparts, use multiple mechanisms to survey class I expression on target cells.

scholarly journals Acquisition of External Major Histocompatibility Complex Class I Molecules by Natural Killer Cells Expressing Inhibitory Ly49 Receptors

2001 ◽  
Vol 194 (10) ◽  
pp. 1519-1530 ◽  
Author(s):  
Anna Sjöström ◽  
Mikael Eriksson ◽  
Cristina Cerboni ◽  
Maria H. Johansson ◽  
Charles L. Sentman ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Nk Cells ◽  
Natural Killer ◽  
Mhc Class I ◽  
Nk Cell ◽  
Indirect Evidence ◽  
Class I ◽  
Target Cells ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

Murine natural killer (NK) cells express inhibitory Ly49 receptors specific for major histocompatibility complex (MHC) class I molecules. We report that during interactions with cells in the environment, NK cells acquired MHC class I ligands from surrounding cells in a Ly49-specific fashion and displayed them at the cell surface. Ligand acquisition sometimes reached 20% of the MHC class I expression on surrounding cells, involved transfer of the entire MHC class I protein to the NK cell, and was independent of whether or not the NK cell expressed the MHC class I ligand itself. We also present indirect evidence for spontaneous MHC class I acquisition in vivo, as well as describe an in vitro coculture system with transfected cells in which the same phenomenon occurred. Functional studies in the latter model showed that uptake of H-2Dd by Ly49A+ NK cells was accompanied by a partial inactivation of cytotoxic activity in the NK cell, as tested against H-2Dd-negative target cells. In addition, ligand acquisition did not abrogate the ability of Ly49A+ NK cells to receive inhibitory signals from external H-2Dd molecules. This study is the first to describe ligand acquisition by NK cells, which parallels recently described phenomena in T and B cells.

Sign in / Sign up

Export Citation Format

Share Document