Cis association of Ly49A with MHC class I restricts natural killer cell inhibition

Doucey, Marie‐Agnès; Scarpellino, Léonardo; Zimmer, Jacques; Guillaume, Philippe; Luescher, Immanuel F.; Bron, Claude; Held, Werner

doi:10.1038/ni1043

Cited by 186 publications

(237 citation statements)

References 48 publications

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“…Ly49 cDNAs in eukaryotic expression vectors have been described before (15,17). Ly49B, C, G2, I, and Q were either subcloned directly or PCR amplified from plasmid DNA and B6 day 14 fetal liver cDNA, respectively, before cloning into a modified pEF-BOS internal ribosome entry site puro expression vector to introduce a NH 2 -terminal vesicular stomatitis virus (VSV) tag.…”

Section: Constructsmentioning

confidence: 99%

“…The following cell lines were used: C1498 (immature NK T cell line (H-2 b ) (18) (provided by W. Seaman, University of California, San Francisco, CA); C1498 transfected with Ly49A, D d , and Ly49A ϩ D d (15); C4.4.25Ϫ (a ␤ 2 m-deficient variant of EL-4 (H-2 b ) (19) (provided by H. G. Ljunggren, Karolinska, Sweden); and RMA/S (TAP-1-deficient). These cell lines were transfected by electroporation.…”

Section: Cells and Transfectantsmentioning

confidence: 99%

“…Transfectants or nylon-wool nonadherent spleen cells were acid stripped as described previously (15). Briefly, the cells were washed twice in PBS and resuspended in citrate buffer (0.133 M citric acid/0.066 M Na 2 HPO 4 ; pH 3.3) at 5 ϫ 10 6 cells/ml for 4 min at room temperature.…”

Section: Acid Treatmentmentioning

confidence: 99%

“…Corresponding results were obtained with the D k -MT multimer (data not shown). To assess whether multimer binding to Ly49A was modulated by the NK cell's own MHC-I, we disrupted MHC-I complexes on the surface of NK cells using a brief exposure to an acidic buffer (15,21). Disruption of MHC-I complexes is demonstrated by the complete loss of mAb staining for ␤ 2 m (Fig.…”

Section: Modulation Of H-2d Multimer Binding By Mhc-i Expressionmentioning

confidence: 99%

“…In addition to an interaction of NK cell receptors with ligand on potential target cells (trans interaction), we have recently shown that Ly49A interacts with its H-2D d ligand expressed on the same cell (cis-interaction) (15 In this study, we have (re)evaluated the MHC-I-binding capacity of all the Ly49 family receptors expressed in B6 mice using MHC-I multimers complexed with mouse ␤ 2 m. In addition, we have analyzed MHC-I multimer binding to NK cells, and finally we have tested whether the modulation of ligand binding by the NK cells' own MHC-I is a common feature of MHC-I-binding Ly49 receptors.…”

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confidence: 99%

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

Scarpellino

Oeschger

Guillaume

et al. 2007

The Journal of Immunology

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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.

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Section: Constructsmentioning

confidence: 99%

Section: Cells and Transfectantsmentioning

confidence: 99%

Section: Acid Treatmentmentioning

confidence: 99%

Section: Modulation Of H-2d Multimer Binding By Mhc-i Expressionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Scarpellino

Oeschger

Guillaume

et al. 2007

The Journal of Immunology

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Natural Killer Cells

Kärre

Kiessling³

2010

Topley &Amp; Wilson's Microbiology and Microbial Infections

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As the name suggests, natural killer (NK) cells are important cells of the immune system "naturally" primed to "kill" malignant or transformed cells and various infectious pathogens. Like other cells of the immune system, these cells play a major role in immuneregulation; however, their uniqueness lies in blurring the gap between innate and adaptive immune response. Natural killer T cells (NKT), also known as innate lymphocytes are recently discovered cells known for their action against lipid antigens. Properties of NK and NK-T cells have been harnessed in recent years for therapeutic and prophylactic medicine in the form of anti-tumour drugs, immunomodulators and vaccines against HIV, Pox virus, Influenza and many more. Knowledge of the mechanism of action and properties of these cells, brighten the possibility for cure of many diseases, the remedy of which still remain unrevealed!

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