Recognition of H-2Kb by Ly49Q suggests a role for class Ia MHC regulation of plasmacytoid dendritic cell function

Tai, Lee-Hwa; Goulet, Marie-Line; Bélanger, Simon; Troke, Angela D.; St‐Laurent, Aaron; Mesci, Aruz; Toyama–Sorimachi, Noriko; Carlyle, James R.; Makrigiannis, Andrew P.

doi:10.1016/j.molimm.2006.12.010

Cited by 23 publications

(31 citation statements)

References 33 publications

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“…As previously reported, L929 tumor cells are unable to stimulate lacZ production by BWZ. Ly49Q BALB or BWZ.Ly49Q B6 reporter cells (23). However, stable expression of H-2K b , but not H-2D b , in L929 was able to stimulate both types of BWZ.Ly49Q reporter cells, but not parental BWZ.36 parental cells, in line with previous findings (Fig.…”

Section: Resultssupporting

confidence: 91%

“…Binding was observed for Ly49G: (22). Similarly, using lacZ-based reporter cell assays, as well as soluble MHC-I tetramers, it was previously reported that the plasmacytoid dendritic cell (pDC)-expressed Ly49Q displays strong H-2K b binding, but apparently no binding to H-2D b or MHC-I alleles expressed in cells from mice possessing H-2 a,q,k,d MHC haplotypes (23). However, since these initial studies there have been new advances in our knowledge of Ly49/MHC-I interactions in the B6 inbred mouse strain, including the role of cis versus trans competitive binding and loss of binding observed when the whole MHC-I tetramer is not mouse derived (24).…”

mentioning

confidence: 60%

“…In particular, BWZ.Ly49Q but not BWZ.36 parental reporter cells were stimulated by cells of the H-2 b haplotype, as well as immobilized recombinant H-2K b . However, BWZ.Ly49Q reporter cells did not respond to cells derived from non-H-2 b mice, B2m 2/2 , H-2K b2/2 H-2D b2/2 mice, nor to recombinant H-2D b (23). To further test the selective binding of Ly49Q we decided to "rescue" a nonstimulating tumor cell, specifically L929 fibroblasts, which bear H-2 k MHC-I molecules, by transfection of H-2K b or H-2D b .…”

Section: Resultsmentioning

confidence: 89%

“…We have previously shown via BWZ reporter cell assays and soluble tetramer analyses that H-2K b is a strong ligand for Ly49Q (23), and via gene-knockout mice that this interaction is key for the production of IFN-a by pDCs (25). In particular, BWZ.Ly49Q but not BWZ.36 parental reporter cells were stimulated by cells of the H-2 b haplotype, as well as immobilized recombinant H-2K b .…”

Section: Resultsmentioning

confidence: 97%

“…Construction of the CD3z/NKR-P1B/Ly49Q chimeric receptor and BWZ assay was described previously (23 . DCs were isolated from collagenase (Roche Diagnostics, Laval, QC, Canada)-treated splenocytes using anti-CD11c-conjugated microbeads (Miltenyi Biotec, Auburn, CA).…”

Section: Cellsmentioning

confidence: 99%

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Optimized Tetramer Analysis Reveals Ly49 Promiscuity for MHC Ligands

McFall

Al-Khattabi

et al. 2013

The Journal of Immunology

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Murine Ly49 receptors, which are expressed mainly on NK and NKT cells, interact with MHC class I (MHC-I) molecules with varying specificity. Differing reports of Ly49/MHC binding affinities may be affected by multiple factors, including cis versus trans competition and species origin of the MHC-I L chain (β2-microglobulin). To determine the contribution of each of these factors, Ly49G, Ly49I, Ly49O, Ly49V, and Ly49Q receptors from the 129 mouse strain were expressed individually on human 293T cells or the mouse cell lines MHC-I–deficient C1498, H-2b–expressing MC57G, and H-2k–expressing L929. The capacity to bind to H-2Db– and H-2Kb–soluble MHC-I tetramers containing either human or murine β2-microglobulin L chains was tested for all five Ly49 receptors in all four cell lines. We found that most of these five inhibitory Ly49 receptors show binding for one or both self–MHC-I molecules in soluble tetramer binding assays when three conditions are fulfilled: 1) lack of competing cis interactions, 2) tetramer L chain is of mouse origin, and 3) Ly49 is expressed in mouse and not human cell lines. Furthermore, Ly49Q, the single known MHC-I receptor on plasmacytoid dendritic cells, was shown to bind H-2Db in addition to H-2Kb when the above conditions were met, suggesting that Ly49Q functions as a pan–MHC-Ia receptor on plasmacytoid dendritic cells. In this study, we have optimized the parameters for soluble tetramer binding analyses to enhance future Ly49 ligand identification and to better evaluate specific contributions by different Ly49/MHC-I pairs to NK cell education and function.

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Section: Resultssupporting

confidence: 91%

mentioning

confidence: 60%

Section: Resultsmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 97%

Section: Cellsmentioning

confidence: 99%

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Optimized Tetramer Analysis Reveals Ly49 Promiscuity for MHC Ligands

McFall

Al-Khattabi

et al. 2013

The Journal of Immunology

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Ly49Q ligand expressed by activated B cells induces plasmacytoid DC maturation

Toma-Hirano

Namiki²,

Shibata³

et al. 2009

Eur J Immunol

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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...

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Inhibitory Ly49 Receptors on Mouse Natural Killer Cells

Orr

Lanier

2010

Current Topics in Microbiology and Immunology

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The Ly49 receptors, which are expressed in a stochastic manner on subsets of murine natural killer (NK) cells, T cells, and other cells, are encoded by the Klra gene family and include receptors with either inhibitory or activating function. All of the inhibitory Ly49 receptors are characterized by an immunoreceptor tyrosine-based inhibitory motif in their cytoplasmic domain, which upon phosphorylation recruits tyrosine or lipid phosphatases to dampen signals transmitted through other activating receptors. Most of the inhibitory Ly49 receptors recognize polymorphic epitopes on major histocompatibility complex (MHC) class I proteins as ligands. Here, we review the polymorphism, ligand specificity, and signaling capacity of the inhibitory Ly49 receptors and discuss how these molecules regulate NK cell development and function.

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Recognition of H-2Kb by Ly49Q suggests a role for class Ia MHC regulation of plasmacytoid dendritic cell function

Cited by 23 publications

References 33 publications

Optimized Tetramer Analysis Reveals Ly49 Promiscuity for MHC Ligands

Optimized Tetramer Analysis Reveals Ly49 Promiscuity for MHC Ligands

Ly49Q ligand expressed by activated B cells induces plasmacytoid DC maturation

Inhibitory Ly49 Receptors on Mouse Natural Killer Cells

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