The NK2.1 receptor is encoded by Ly-49C and its expression is regulated by MHC class I alleles

Gosselin, Pierre; Lusignan, Y; Brennan, Jack; Takei, Fumio; Lemieux, Suzanne

doi:10.1093/intimm/9.4.533

Cited by 27 publications

(28 citation statements)

References 8 publications

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“…Biotinylated anti-Ly49C (4LO3311) has been described previously. 36 Anti-NK1.1-phycoerythrin (PE) or peridinin chlorophyll-alpha protein (PerCP)-cyanin 5.5 (Cy5.5), anti-CD3-CyChrome, anti-interferon-␥ (IFN-␥)-FITC, antiLy49I-biotin (YLI-90), anti-CD11b-FITC, anti-CD16-FITC, 2B4-FITC, DX5-FITC, 2F1-FITC, 37 anti-Ly5.1-PE, and streptavidin-PE were purchased from Pharmingen (San Diego, CA). Streptavidin-PE-Texas red (TR) was purchased from Caltag Laboratories (Burlingame, CA).…”

Section: Staining Protocolsmentioning

confidence: 99%

A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules

Fernandez

Treiner

Vance

et al. 2005

Blood

488

569

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It is widely believed that self-tolerance of natural killer (NK) cells occurs because each NK cell expresses at least one inhibitory receptor specific for a host major histocompatibility complex (MHC) class I molecule. Here we report that some NK cells lack all known self-MHC-specific inhibitory receptors, yet are nevertheless self-tolerant. These NK cells exhibit a normal cell surface phenotype and some functional activity. However, they respond poorly to class I-deficient normal cells, tumor cells, or cross-linking of stimulatory receptors, suggesting that self-tolerance is established by dampening stimulatory signaling. Thus, self- IntroductionNatural killer (NK) cells attack transformed, infected, and allogeneic cells. Target cell recognition depends on stimulatory receptors with various specificities and inhibitory receptors specific for major histocompatibility complex (MHC) class I molecules. [1][2][3] The stimulatory receptors associate with signaling adapter molecules including DNAX activating protein 12 (DAP12), CD3, or Fc receptor ␥ (FcR␥), which contain immunoreceptor tyrosine-based activation motifs (ITAMs), whereas the inhibitory receptors contain cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The balance of stimulatory and inhibitory signaling determines whether target cells are lysed and stimulate cytokine production.NK stimulatory receptors 3 recognize pathogen-encoded molecules (eg, Ly49H ligand 4,5 ) or host molecules that are up-regulated in transformed or infected cells (eg, NKG2D ligands 6 ). Because NK cells attack certain uninfected and untransformed cell types, such as bone marrow cells or lymphoblasts from MHC-deficient or allogeneic animals, it is believed that even these normal cells express a ligand that is recognized by an NK stimulatory receptor (reviewed in Raulet et al 7 ).There are 3 different families of MHC-specific inhibitory receptors that have been defined: Ly49, a family of approximately 10 lectinlike receptors expressed by murine NK cells 8 ; killer immunoglobulin (Ig)-like receptors (KIRs), a family of approximately 10 Ig-like receptors expressed by human NK cells 2,9 ; and CD94/NKG2A, a lectinlike receptor heterodimer expressed by both human and murine NK cells. 10,11 Ly49 receptors and KIRs bind to classical class Ia MHC molecules. In contrast, CD94/ NKG2A interacts with a nonclassical class Ib molecule called Qa-1 in mice and HLA-E in humans. The Qa-1/HLA-E molecules are ␤2-microglobulin (␤2m)-dependent and present a conserved peptide from the cleaved signal sequences of certain class Ia MHC molecules, which is recognized by CD94/NKG2A. Therefore, the CD94/NKG2A receptor indirectly recognizes class Ia molecules. All 3 types of inhibitory NK receptors distinguish subgroups of MHC class I molecules and all are expressed in a variegated fashion such that each NK cell expresses a more or less random set of receptors, with an average number per cell of 2 to 3. 12,13 Whether a target cell inhibits a given NK cell depends on whether the NK cell express...

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Section: Staining Protocolsmentioning

confidence: 99%

A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules

Fernandez

Treiner

Vance

et al. 2005

Blood

488

569

View full text Add to dashboard Cite

show abstract

“…The following mAbs were used: anti-CD3 (145-2C11), anti-NK1.1 (PK136), anti-NKp46 (29A1.4), anti-2B4 (m2B4(B6)458.1), anti-KLRG1 (2F1/KLRG1), anti-Ly49G2 (4D11), and anti-Ly49A (YEI/48) (all from BioLegend); anti-CD1d (1B1), antiCD49b (Dx5), anti-Ly49D (4E5), anti-NKG2D (CX5), and anti-CD27 (LG.3A10) (all from BD Pharmingen); anti-CD11b (M1/70.15), Streptavidin-QD605, and Streptavidin-RED670 (Invitrogen Molecular Probes); and anti-NKG2A/C/E (20d5) (AdB Serotec). The anti-Ly49C (4LO331) hybridoma was a kind gift from Suzanne Lemieux (Institut Armand Frappier) (27,28) and was used in combination with anti-mouse IgG3 (Southern Biotechnology). Dead cells were excluded using the Live/DEAD Fixable Aqua Dead cell stain kit (Invitrogen Molecular Probes).…”

Section: Abs and Facs Analysismentioning

confidence: 99%

A Genetic Defect in Mice That Impairs Missing Self Recognition Despite Evidence for Normal Maturation and MHC Class I–Dependent Education of NK Cells

Wickström

Öberg

Kärre

et al. 2014

The Journal of Immunology

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In studies of a CD1d1-deficient mouse strain, we unexpectedly observed a severely impaired capacity for NK cell–mediated rejection of MHC class I–deficient (spleen or tumor) cells. Studies of another CD1-defective strain, as well as intercrosses with C57BL/6 mice, indicated that the impaired missing self rejection (IMSR) NK cell defect was a recessive trait, independent from the targeted CD1 locus. Studies with mixed bone marrow chimeras indicated that the defect is intrinsic to NK cells. The IMSR mice had normal proportions of NK cells, displaying a typical cell surface phenotype, as evaluated using a panel of Abs to developmental markers and known receptors. The impaired missing self recognition could not be overcome through cytokine stimulation. There was also an impaired capacity with respect to NKG2D-dependent cytotoxicity, whereas the mice exhibited normal Ly49D/DAP12-dependent responses in vivo and in vitro. The NK cell system of IMSR mice showed two hallmarks of MHC-dependent education: skewing of the Ly49 receptor repertoire and differential in vitro responsiveness between NK cells with and without inhibitory receptors for self-MHC (“licensing”). We conclude that these mice have a recessive trait that perturbs the missing self reaction, as well as NKG2D-dependent responses, whereas other aspects of the NK system, such as development, capacity to sense MHC molecules during education, and Ly49D/DAP12-dependent responses, are largely intact.

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“…Ly49C is normally expressed on ϳ30 -35% of NK cells and on a few percent of NK T cells in B6 mice (34,45). Several different MHC class I molecules, in particular H-2K b , have been shown to be a ligand for Ly49C.…”

Section: Ly49c-transgenic Mice Express a Functional Transgene On All mentioning

confidence: 99%

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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The NK2.1 receptor is encoded by Ly-49C and its expression is regulated by MHC class I alleles

Cited by 27 publications

References 8 publications

A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules

A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules

A Genetic Defect in Mice That Impairs Missing Self Recognition Despite Evidence for Normal Maturation and MHC Class I–Dependent Education of NK Cells

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

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