The balancing act: Inhibitory Ly49 regulate NKG2D-mediated NK cell functions

Malarkannan, Subramaniam

doi:10.1016/j.smim.2006.04.002

Cited by 25 publications

(25 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A set of these molecules is recognized by the NKG2D activating receptor, which has been considered a dominant activating receptor, such that triggering of NKG2D can induce cytotoxic lysis of the stressed target cells expressing ligands for NKG2D, despite the expression of normal levels of MHC class I molecules 7,8 . The current consensus is that NK cell activation and cytotoxicity result from the integration of signals produced by ‘missing self’ and ‘induced self’ interactions and a shifting of the balance in the signalling strength between the inhibitory and activating receptors (reviewed by Malarkannan 9 ).…”

Section: Introductionmentioning

confidence: 99%

Regulation of ligands for the activating receptor NKG2D

2007

View full text Add to dashboard Cite

Summary The outcome of an encounter between a cytotoxic cell and a potential target cell depends on the balance of signals from inhibitory and activating receptors. Natural Killer group 2D (NKG2D) has recently emerged as a major activating receptor on T lymphocytes and natural killer cells. In both humans and mice, multiple different genes encode ligands for NKG2D, and these ligands are non‐classical major histocompatibility complex class I molecules. The NKG2D–ligand interaction triggers an activating signal in the cell expressing NKG2D and this promotes cytotoxic lysis of the cell expressing the ligand. Most normal tissues do not express ligands for NKG2D, but ligand expression has been documented in tumour and virus‐infected cells, leading to lysis of these cells. Tight regulation of ligand expression is important. If there is inappropriate expression in normal tissues, this will favour autoimmune processes, whilst failure to up‐regulate the ligands in pathological conditions would favour cancer development or dissemination of intracellular infection.

show abstract

Section: Introductionmentioning

confidence: 99%

Regulation of ligands for the activating receptor NKG2D

2007

View full text Add to dashboard Cite

show abstract

“…Natural cytotoxicity and cytokine/chemokine production are 2 primary effector functions of NK cells. Both of these functions are regulated precisely through NK cell activation and inhibitory receptors such as NKG2D activation receptor and Ly49 inhibitory receptor [33,34]. The interaction with the corresponding ligands ultimately results in signaling transductions into the nucleus that converge into the decision of whether to execute NK functions.…”

Section: Nk Cell Anti-influenza Activation Receptorsmentioning

confidence: 99%

“…NK cell function is balanced by signals from activating and inhibitory receptors [33,69]. NK cell-activating receptors recognize their ligands, which are usually not present in the normal self cells but rather, in targets under infection or tumori-genesis.…”

Section: Escape Of Nk Recognition By Reorganizing Mhc Imentioning

confidence: 99%

Evasion of natural killer cells by influenza virus

Guo

Kumar

Malarkannan

2010

Journal of Leukocyte Biology

Self Cite

View full text Add to dashboard Cite

NK cells are important innate immune effectors during influenza virus infection. However, the influenza virus seems able to use several tactics to counter NK cell recognition for immune evasion. In this review, we will summarize and discuss recent advances regarding the understanding of NK cell evasion mechanisms manipulated by the influenza virus to facilitate its rapid replication inside the respiratory epithelial cells.

show abstract

“…For example, Ly49H binds the m157 gene product of mouse cytomegalovirus [19,20]. A fine balance between inhibitory and activating signals regulates the cytokine production and cytolytic activity of NK cells [21][22][23].The presence of an ITIM in the cytoplasmic domain of Ly49Q suggests that it -like the Ly49 family members expressed on NK cells -might function as an inhibitory receptor. with an increasing ability of Ly49Q-FcM to bind to the cells ( Fig.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Ly49Q ligand expressed by activated B cells induces plasmacytoid DC maturation

Toma-Hirano

Namiki²,

Shibata³

et al. 2009

Eur J Immunol

View full text Add to dashboard Cite

Ly49Q, a type II C-type lectin expressed on mouse plasmacytoid DC (pDC), contains a single carbohydrate recognition domain in its extracellular region and an ITIM in its cytoplasmic domain. We have identified the MHC class I molecule H-2K b as a Ly49Q ligand, confirming prior reports. Although H-2K b is expressed on essentially all hematopoietic cells, we found that only CpG-stimulated B cells were able to activate Ly49Q. This discovery correlated with our finding that although H-2K b forms clusters on CpG-activated B cells, it is diffusely expressed on resting B cells. Furthermore, CpG-stimulated, but not resting, B cells up-regulated co-stimulatory molecules on pDC. This finding was confirmed by the fact that binding by anti-Ly49Q mAb to Ly49Q led to pDC maturation in vitro. Our results suggest that clustered H-2K b on activated B cells act as ligands for Ly49Q and induce pDC maturation in vitro.Key words: B cell . IFN . Ly49Q . MHC class I . plasmacytoid DC Supporting Information available online IntroductionPlasmacytoid DC (pDC) are a specialized subset of DC responsible for initiating immune responses to viruses [1,2]. They develop in the bone marrow and circulate in the blood before migrating into lymphoid and non-lymphoid organs [1,2], and they exhibit increased recruitment into sites of inflammation [3,4]. pDC detect viruses through TLR7 and TLR9 [5]. In response, they produce large amounts of type I IFN and pro-inflammatory chemokines to direct the innate and adaptive immune responses and to promote cytotoxicity in NK cells and CD8 1 T cells [6]. pDC have also been implicated in promoting monocyte-derived DC maturation, presenting antigen to T cells, inducing Th1 polarization [1,2], and promoting B-cell differentiation into 1344Ab-producing plasma cells [7,8]. However, there is very little information about how other cells affect pDC function.Ly49Q is a member of the Ly49 family of mouse NK receptors that is expressed on pDC but not on NK cells or NKT cells [9][10][11]. This receptor family belongs to a group of type II integral membrane proteins that contain external domains homologous to the super-family of Ca-dependent lectins [12]. The Ly49 family comprises two subclasses, one of which harbors an ITIM in the cytoplasmic domain, which recruits the intracellular tyrosine phosphatases SHP-1 or SHP-2 [13][14][15]. Members of the other subclass lack an ITIM, have a charged residue in the transmembrane domain, and deliver activating signals via the adapter protein DAP12 [16]. Inhibitory Ly49 molecules primarily bind MHC class I ligands [17,18], whereas the ligands for activating Ly49 molecules also include MHC class I-like molecules expressed by viruses. For example, Ly49H binds the m157 gene product of mouse cytomegalovirus [19,20]. A fine balance between inhibitory and activating signals regulates the cytokine production and cytolytic activity of NK cells [21][22][23].The presence of an ITIM in the cytoplasmic domain of Ly49Q suggests that it -like the Ly49 family members expressed on NK cells -might f...

show abstract

The balancing act: Inhibitory Ly49 regulate NKG2D-mediated NK cell functions

Cited by 25 publications

References 75 publications

Regulation of ligands for the activating receptor NKG2D

Regulation of ligands for the activating receptor NKG2D

Evasion of natural killer cells by influenza virus

Ly49Q ligand expressed by activated B cells induces plasmacytoid DC maturation

Contact Info

Product

Resources

About