Visualization of inhibitory Ly49 receptor specificity with soluble major histocompatibility complex class I tetramers

Michaëlsson, Jakob; Achour, Adnane; Salcedo, Margarita; Kåse-Sjöström, Anna; Sundbäck, Jonas; Harris, R. Adron; Kärre, Klas

doi:10.1002/1521-4141(200001)30:1<300::aid-immu300>3.0.co;2-s

Cited by 72 publications

(62 citation statements)

References 40 publications

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“…9D), as previously observed by Kambayashi et al [26]. The fact that FasL expression was inhibited on only in a subpopulation of the NK cells was entirely as expected, since only a subpopulation of all NK cells expresses inhibitory receptors recognizing H-2D b [27]. Taken together, this observation provides a possible mechanism for the regulation of perforinindependent NK cell-mediated cytotoxicity.…”

Section: Mhc Class I-mediated Inhibiting Signals Abrogate Up-regulatisupporting

confidence: 87%

Regulation of perforin‐independent NK cell‐mediated cytotoxicity

et al. 2003

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Natural killer (NK) cells have been thought to depend largely on perforin-mediated mechanisms for the induction of cell death in targets. However, this view has more recently been challenged. It is now clear that NK cells are capable of using death ligands like Fas ligand (FasL) or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to induce cytotoxicity. Still, relatively little is known about the control of these "perforin-independent" cell death eliciting reactions, for example, the regulation of FasL expression on NK cells. In the present study, we confirm the ability of NK cells to mediate target cytotoxicity in the absence of perforin, in vivo and in vitro. We show that the induction of perforin-independent NK cellmediated cell death is prevented by inhibiting signals mediated by MHC class I recognition. Furthermore, we demonstrate in vitro that cross-linking of the activation receptor NK1.1 on NK cells leads to the up-regulation of FasL on the cell surface. However, simultaneous engagement of an MHC class I binding inhibitory receptor prevents the externalization of FasL. These results provide a mechanistic explanation for the MHC class I-dependent regulation of perforin-independent cytotoxicity.

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Section: Mhc Class I-mediated Inhibiting Signals Abrogate Up-regulatisupporting

confidence: 87%

Regulation of perforin‐independent NK cell‐mediated cytotoxicity

et al. 2003

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“…Receptor downmodulation on NK cells from mice expressing single MHC-Ia molecules, as previously reported (32), may still be the best way to determine Ly49/MHC-I specificity for the above reasons. This assay shows that Ly49A surface expression on NK cells from H-2D b single MHC-I transgenic mice is significantly lower than NK cells from B2m 2/2 mice (32), in agreement with mouse b 2 m tetramer studies (24,28). However, it is possible that binding affinity and surface downmodulation do not always go hand in hand.…”

Section: Discussionsupporting

confidence: 69%

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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“…There was also a decrease in Ly49A expression. Data using tetramers suggest that Ly49A can bind to H-2D b but not to H-2K b (18). Thus, our data indicate that it is the interaction of the transgene with MHC that results in a decrease in the expression of other Ly49 receptors, whether they have an MHC ligand or not.…”

Section: Discussionmentioning

confidence: 63%

MHC Class I-Ly49 Interactions Shape the Ly49 Repertoire on Murine NK Cells

Fahlén

Lendahl

Sentman

2001

The Journal of Immunology

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This study aims to determine how the interaction of Ly49 receptors with MHC class I molecules shapes the development of the Ly49 repertoire. We have examined the percentage of NK cells that expressed Ly49A, Ly49G2, and Ly49D in single and double Ly49A/C-transgenic mice on four different MHC backgrounds, H-2b, H-2d, H-2b/d, and β2-microglobulin−/−. The results show that the total numbers of NK cells were not different among the strains. The prior expression of a Ly49 receptor capable of binding to self MHC class I altered the percentage of NK cells expressing endogenous Ly49A, Ly49G2, and Ly49D even in mice in which no MHC ligand was present for the latter receptors. The NK cells in the Ly49-transgenic mice expressed the same level of endogenous Ly49 receptors as wild-type mice of a similar MHC background. In contrast, the number of NK T cells was reduced in mice in which the Ly49 transgene could bind to a MHC class I molecule. The onset of Ly49 receptor expression on NK cells during ontogeny was not altered in the presence of transgenic Ly49 receptors. These data support a sequential model and argue against a selection model for Ly49 repertoire development on NK cells.

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Visualization of inhibitory Ly49 receptor specificity with soluble major histocompatibility complex class I tetramers

Cited by 72 publications

References 40 publications

Regulation of perforin‐independent NK cell‐mediated cytotoxicity

Regulation of perforin‐independent NK cell‐mediated cytotoxicity

Optimized Tetramer Analysis Reveals Ly49 Promiscuity for MHC Ligands

MHC Class I-Ly49 Interactions Shape the Ly49 Repertoire on Murine NK Cells

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