Ly49Q, a member of the Ly49 family that is selectively expressed on myeloid lineage cells and involved in regulation of cytoskeletal architecture

Self Cite

Using a novel mAb specific for mouse Ly49B, we report here that Ly49B, the last remaining member of the C57 Ly49 family to be characterized, is expressed at low levels on ∼1.5% of spleen cells, none which are NK cells or T cells but which instead belong to several distinct subpopulations of myeloid cells defined by expression of CD11b and different levels of Gr1. Much larger proportions of bone marrow and peritoneal cells expressed Ly49B, all being CD11b+ and comprising multiple subpopulations defined by light scatter, F4/80, and Gr1 expression. Costaining for Ly49Q, also expressed on myeloid cells, revealed that Ly49B and Ly49Q were most strongly expressed on nonoverlapping subpopulations, Ly49Qhigh cells being mostly B220+CD4+ and/or CD8+, Ly49B+ cells lacking these markers. Myeloid populations that developed from bone marrow progenitors in vitro frequently coexpressed both Ly49B and Ly49Q, and Ly49B expression could be up-regulated by LPS, α-IFN, and γ-IFN, often independently of Ly49Q. PCR analysis revealed that cultured NK cells and T cells contained Ly49B transcripts, and Ly49B expression could be detected on NK cells cultured in IL-12 plus IL-18, and on an immature NK cell line. Immunohistochemical studies showed that Ly49B expression in tissues overlapped with but was distinct from that of all other myeloid molecules examined, being particularly prominent in the lamina propria and dome of Peyer’s patches, implicating an important role of Ly49B in gut immunobiology. In transfected cells, Ly49B was found to associate with SHP-1, SHP-2, and SHIP in a manner strongly regulated by intracellular phosphorylation events.

Section: Comparative Expression Of Ly49b and Ly49qcontrasting

confidence: 40%

Ly49B Is Expressed on Multiple Subpopulations of Myeloid Cells

Gays¹,

Aust²,

Reid

et al. 2006

Self Cite

“…Ly49Q is expressed on myeloid lineage cells, in particular plasmacytoid dendritic cells (4,31). Thus, cell types other than NK cells use receptor masking to adapt receptor accessibility and consequently receptor function to self-MHC-I.…”

Section: Ly49b and Ly49qmentioning

confidence: 99%

“…In C57BL/6 (B6) mice, 14 Ly49 genes have been identified, four of which are pseudogenes (2). Whereas the majority of the Ly49 receptors are expressed by NK cells, Ly49B and Ly49Q, which are located at either end of the Ly49 gene complex, are not expressed by NK cells (3,4). Rather, Ly49Q is found on myeloid lineage cells (4).…”

mentioning

confidence: 99%

“…Whereas the majority of the Ly49 receptors are expressed by NK cells, Ly49B and Ly49Q, which are located at either end of the Ly49 gene complex, are not expressed by NK cells (3,4). Rather, Ly49Q is found on myeloid lineage cells (4). Based on structural criteria and/or functional data, eight of the Ly49 family receptors in B6 mice are inhibitory, whereas two family members, Ly49D and Ly49H, activate NK cells.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Interactions of Ly49 Family Receptors with MHC Class I Ligands in trans and cis

Scarpellino

Oeschger

Guillaume

et al. 2007

The Ly49A NK cell receptor interacts with MHC class I (MHC-I) molecules on target cells and negatively regulates NK cell-mediated target cell lysis. We have recently shown that the MHC-I ligand-binding capacity of the Ly49A NK cell receptor is controlled by the NK cells’ own MHC-I. To see whether this property was unique to Ly49A, we have investigated the binding of soluble MHC-I multimers to the Ly49 family receptors expressed in MHC-I-deficient and -sufficient C57BL/6 mice. In this study, we confirm the binding of classical MHC-I to the inhibitory Ly49A, C and I receptors, and demonstrate that detectable MHC-I binding to MHC-I-deficient NK cells is exclusively mediated by these three receptors. We did not detect significant multimer binding to stably transfected or NK cell-expressed Ly49D, E, F, G, and H receptors. Yet, we identified the more distantly related Ly49B and Ly49Q, which are not expressed by NK cells, as two novel MHC-I receptors in mice. Furthermore, we show using MHC-I-sufficient mice that the NK cells’ own MHC-I significantly masks the Ly49A and Ly49C, but not the Ly49I receptor. Nevertheless, Ly49I was partly masked on transfected tumor cells, suggesting that the structure of Ly49I is compatible in principal with cis binding of MHC-I. Finally, masking of Ly49Q by cis MHC-I was minor, whereas masking of Ly49B was not detected. These data significantly extend the MHC-I specificity of Ly49 family receptors and show that the accessibility of most, but not all, MHC-I-binding Ly49 receptors is modulated by the expression of MHC-I in cis.

“…Additionally, two Ly49, Ly49B and Ly49Q, are expressed on myeloid-derived cells, including macrophages, neutrophils, and DCs (6,7). Initial cDNA screening of inbred mouse strains revealed extreme genetic diversity and polymorphism in different mouse strains (8), which was later revealed to be a result of genomic plasticity within the Ly49 region resulting in cluster sizes ranging from 8 to 22 Ly49 genes (9,10).…”

mentioning

confidence: 99%

Optimized Tetramer Analysis Reveals Ly49 Promiscuity for MHC Ligands

McFall

Al-Khattabi

et al. 2013

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.