Rat natural killer cell receptor systems and recognition of MHC class I molecules

Rolstad, Bent; Naper, Christian; Løvik, Guro; Vaage, John T.; Ryan, James C.; Bäckman‐Petersson, Eva; Kirsch, Ralf D.; Butcher, Geoffrey W.

doi:10.1034/j.1600-065x.2001.1810112.x

Cited by 35 publications

(28 citation statements)

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“…If Ly-49G BALB/c recognizes a rat MHC ligand, then a nonclassical molecule encoded in the RT1.C/ E/M region of the RT1 1 haplotype may be a ligand. Rat nonclassical class I molecules encoded in the RT1.C/E/M region of RT1 l can activate or inhibit rat NK cell function (43)(44)(45). The significance of xenoantigen recognition by Ly-49 receptors is not understood but could relate to interspecies predation and resistance to pathogen passage across species (16,46).…”

Section: Discussionmentioning

confidence: 99%

Allelic Variation in the Ectodomain of the Inhibitory Ly-49G2 Receptor Alters Its Specificity for Allogeneic and Xenogeneic Ligands

Silver

Lavender

Gong

et al. 2002

The Journal of Immunology

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The Ly-49 multigene receptor family regulates mouse NK cell functions. A number of Ly-49 genes exhibit allelic variation, but the functional significance of allelic differences in extracellular domains of Ly-49 receptors regarding ligand specificity is largely unknown. Amino acid differences exist in the extracellular domains of the B6 and BALB/c allele products of the inhibitory Ly-49G receptor. We constructed chimeric Ly-49 receptors consisting of common cytoplasmic and transmembrane regions of the activating Ly-49W receptor fused with the ectodomains of the B6 and BALB/c alleles of Ly-49G. Expression of these chimeras in the RNK-16 rat NK cell line allowed us to study the specificity of inhibitory receptor ectodomains as they stimulated NK lytic activity. We found that the ectodomain of the BALB/c allele of Ly-49G recognizes both H-2Dd and Dk class I MHC alleles, whereas the ectodomain of the B6 allele of Ly-49G recognizes Dd, and not Dk. The specificity for Dk as well as Dd of the wild-type Ly-49GBALB/c allele product was confirmed with RNK-16 transfectants of this inhibitory receptor. Furthermore, the ectodomain of the Ly-49GBALB/c allele recognizes a distinct repertoire of xenogeneic ligands that only partially overlaps with that recognized by Ly-49GB6. Our results indicate that allelic variation in Ly-49 extracellular domains can have functional significance by altering Ly-49 receptor specificity for mouse class I MHC and xenogeneic ligands.

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Section: Discussionmentioning

confidence: 99%

Allelic Variation in the Ectodomain of the Inhibitory Ly-49G2 Receptor Alters Its Specificity for Allogeneic and Xenogeneic Ligands

Silver

Lavender

Gong

et al. 2002

The Journal of Immunology

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“…Natural killer (NK) cells are large granular lymphocytes with the ability to spontaneously lyse certain tumor cells, virally infected cells or normal, MHC disparate cells [1][2][3]. NK cells express both activating and inhibitory receptors.…”

Section: Introductionmentioning

confidence: 99%

NKp46 defines a subset of bovine leukocytes with natural killer cell characteristics

et al. 2004

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Natural killer (NK) cells have not previously been precisely identified or characterized in cattle or any other ruminant species. We have generated a monoclonal antibody against bovine NKp46, which is expressed exclusively by NK cells in man. NKp46 + cells comprised 1-10% of blood mononuclear cells in cattle, and did not stain with antibodies against CD3, CD4, TCR1, B cell or granulocyte markers. The majority of the NKp46 + cells expressed CD2, and a variable fraction also expressed CD8. The tissue distribution of NKp46 + cells in cattle was compatible with the tissue distribution of NK cells in other species. Bovine NKp46 + cells had typical, large granular lymphocyte morphology, and proliferated vigorously in response to bovine IL-2 for a limited number of cell divisions. IL-2-activated NKp46 + cells killed the bovine kidney cell line MDBK. This cytotoxicity was inhibited by preincubation with antibody against NKp46. In a redirected lysis assay, IL-2-activated NKp46 + cells killed the Fc + R + target cell line P815 after preincubation with antibody against NKp46. Together, these data indicate that bovine NKp46 is an activating receptor and demonstrate the existence of a subset of leukocytes in cattle that, in terms of surface markers, morphology and function, represent NK cells.

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“…Interactions between NK cells and potential target cells occur through a myriad of activating and inhibitory receptors of lectin-like and Ig-related receptor families expressed on the NK cell surface (2). In murine species, such as the rat and mouse, these include members of the Ly49 lectin-like receptor family (3)(4)(5).…”

mentioning

confidence: 99%

“…Both activating and inhibitory Ly49 receptor types are found, with some activating/inhibitory hybrid receptors identified in the rat (7). Class I MHC (MHC I) 3 is the ligand for most well-studied activating and inhibitory murine Ly49 (4,13). Additionally, the viral MHC I homologue, m157 from mouse CMV, is a ligand for the mouse-activating Ly49H and inhibitory Ly49I receptors (14).…”

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confidence: 99%

Distinctive Interactions at Multiple Site 2 Subsites by Allele-Specific Rat and Mouse Ly49 Determine Functional Binding and Class I MHC Specificity

Lavender

Chau

Kane

2007

The Journal of Immunology

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Rodent Ly49 exhibit allele-specific MHC I recognition, yet the interaction site, site 2, encompassing the area below the MHC peptide-binding groove, the α3 domain, and associated β2 microglobulin, is highly conserved among rat and mouse MHC I alleles. We previously demonstrated that allele-specific Ly49 recognition can be affected by polymorphisms specifically in the peptide anchor-binding and supertype-defining B pocket of MHC I, possibly through differential conformations assumed by solvent-exposed interaction residues when articulating with this pocket. Through mutagenesis of RT1-A1c and H-2Dd, we map for the first time the interaction site(s) on rat MHC I mediating rat Ly49i2 recognition and the previously unexamined Ly49GBALB/c interaction with H-2Dd. We demonstrate that rat Ly49i2 and mouse Ly49G use both unique and common interactions at three MHC I H chain subsites to mediate functional binding and allele-specific recognition. We find that the F subsite, formed by solvent-exposed residues below the more conserved C-terminal anchor residue-binding F pocket, acts as an anchoring location for both Ly49i2 and Ly49G, whereas these receptors exhibit distinctive reliance on solvent-exposed residues articulating with the polymorphic anchor-binding and supertype-defining pocket(s) at subsite B, as well as on interaction residues at subsite C in the MHC I α3 domain. Our findings, combined with previous Ly49A/H-2Dd and Ly49C/H-2Kb cocrystal data, suggest how allele-specific MHC I conformations and Ly49 polymorphisms may affect Ly49 placement on MHC I ligands and residue usage at site 2, thereby mediating allele-specific recognition at the highly conserved MHC I interface.

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Rat natural killer cell receptor systems and recognition of MHC class I molecules

Cited by 35 publications

References 1 publication

Allelic Variation in the Ectodomain of the Inhibitory Ly-49G2 Receptor Alters Its Specificity for Allogeneic and Xenogeneic Ligands

Allelic Variation in the Ectodomain of the Inhibitory Ly-49G2 Receptor Alters Its Specificity for Allogeneic and Xenogeneic Ligands

NKp46 defines a subset of bovine leukocytes with natural killer cell characteristics

Distinctive Interactions at Multiple Site 2 Subsites by Allele-Specific Rat and Mouse Ly49 Determine Functional Binding and Class I MHC Specificity

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