Ly-49 receptor expression and functional analysis in multiple mouse strains

Ortaldo, John R.; Mason, Anna; Winkler‐Pickett, Robin; Raziuddin, Arati; Murphy, William J.; Mason, Llewellyn H.

doi:10.1002/jlb.66.3.512

Cited by 49 publications

(48 citation statements)

References 30 publications

(37 reference statements)

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“…However, more importantly, we found that the ectodomain of the BALB/c Ly-49G allele confers the gain of specificity for another class I ligand, H-2D k , as well as conferring recognition of a distinct and only partially overlapping repertoire of xenogeneic ligands compared with the B6 allele. The recognition of another ligand, mouse L d , by Ly-49G is somewhat controversial, being observed in some experimental systems (12,34), but not others (29,35). In our experiments, L d was recognized relatively weakly by both Ly-49G allele products and the limited extent of interaction could explain why its recognition by Ly-49G is observed in some experimental systems but not others.…”

Section: Discussioncontrasting

confidence: 45%

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: Discussioncontrasting

confidence: 45%

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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“…Most studies of Ly-49 gene family members have used the B6 strain as a prototype. It is clear from recent studies, however, that the diversity and expression of Ly-49 members can differ among strains (44). Furthermore, complex hybridization patterns obtained in Southern blot analyses of genomic DNA from multiple inbred mouse strains using Ly-49A and Ly-49C cDNA probes suggest that additional Ly-49 members may exist (24).…”

Section: Predicted Amino Acid Sequences Of Ly-49a Ly-49d and Ly-49pmentioning

confidence: 99%

“…To determine whether these receptors may be expressed by NK cells of the NOD mouse, we performed three-color FACS analysis on freshly isolated NWNA and IL-2-activated NOD spleen cells. Because the NOD mouse strain does not express the NK1.1 epitope, we used the DX5 Ab to identify NK cells (3,44). DX5 ϩ CD3 Ϫ cells (Fig.…”

Section: Expression Of A1 and Ye1/48 Epitopes By Nod Nk Cellsmentioning

confidence: 99%

Ly-49P Activates NK-Mediated Lysis by Recognizing H-2Dd 1

Silver

Gong

Chang

et al. 2000

The Journal of Immunology

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Little is known regarding the ligand specificity of Ly-49 activating receptor subfamily members expressed by NK cells. A new Ly-49 activating receptor related to Ly-49A in its extracellular domain, designated Ly-49P, was recently cloned from 129 strain mice. We independently cloned an apparent allele of Ly-49P expressed by nonobese diabetic and nonobese diabetes-resistant mouse strain NK cells. We found it to be reactive with the A1 Ab thought to recognize a polymorphic epitope expressed only by the Ly-49A inhibitory receptor of the C57BL/6 strain. Rat RNK-16 cells transfected with Ly-49P mediated reverse Ab-dependent cellular cytotoxicity of FcR-positive target cells, indicating that Ly-49P can activate NK-mediated lysis. We determined that RNK-16 lysis of Con A blasts induced by Ly-49P was MHC dependent, resulting in efficient lysis of H-2Dd-bearing targets. We found that the Dd α1/α2 domain is required for Ly-49P-mediated RNK-16 activation, as determined by exon shuffling and transfection. Thus, Ly-49P is the second activating Ly-49 receptor demonstrated to induce NK cytotoxicity by recognizing a class I MHC molecule.

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“…1,2 With respect to surface receptor phenotype, BALB/c and B6 NK cell subsets share some NK cell-specific mAb staining since they both react with the YE1/48 (Ly49A), 5E6 (Ly49C/I), and 4D11 (Ly49G) antibodies. 3 In contrast, B6 and not BALB/c NK cells are 4E5 þ (Ly49D), NK1.1 þ (Nkrp1c), and also possess a 5E6 À 1F8 þ (Ly49H) population. [3][4][5] Cloning and sequencing of Ly49 cDNAs showed that BALB/c NK cells share at least three Ly49-related sequences or alleles with B6 mice: Ly49a, c, and g, although the alleles have diverged and contain a significant number of differences, resulting in several amino-acid substitutions.…”

Section: Introductionmentioning

confidence: 97%

“…3 In contrast, B6 and not BALB/c NK cells are 4E5 þ (Ly49D), NK1.1 þ (Nkrp1c), and also possess a 5E6 À 1F8 þ (Ly49H) population. [3][4][5] Cloning and sequencing of Ly49 cDNAs showed that BALB/c NK cells share at least three Ly49-related sequences or alleles with B6 mice: Ly49a, c, and g, although the alleles have diverged and contain a significant number of differences, resulting in several amino-acid substitutions. [6][7][8] The novel activating Ly49L receptor was also found to be expressed in BALB/c mice, but was first identified in the Ly49 haplo-identical CBA and C3H mouse strains.…”

Section: Introductionmentioning

confidence: 97%

Complete elucidation of a minimal class I MHC natural killer cell receptor haplotype

Dewar

Ml³

et al. 2005

Genes Immun

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The BALB/c inbred mouse is widely used in models of infectious disease, transplantation, and cancer. The differences in the immune responses of BALB/c compared to C57BL/6 mice are especially valuable for the identification of immune regulation genes. One striking immune variance between these mice is in the function of natural killer (NK) cells, and there is strong evidence implicating differential expression of Ly49 genes. In this study, the complete BALB/c Ly49 gene cluster has been sequenced and found to contain six functional genes and two pseudogenes. Compared to C57BL/6 mice, there is a 200 kb region absent in the BALB/c cluster including a complete lack of Ly49h-related genes, which explains the increased susceptibility of BALB/c to cytomegalovirus infection. In addition, there is no BALB/c Ly49d allele, explaining the inability of BALB/c NK cells to kill certain tumor cells. The Ly49 region has now been sequenced in three different inbred mouse strains, and comparisons indicate that the evolution of each haplotype is not straightforward and has involved large-scale deletions/ insertions, gene recombination, and unequal crossing over between divergent haplotypes. This study confirms that relatively small murine class I MHC receptor haplotypes exist, analogous to observations made of human killer cell Ig-like receptor gene haplotypes.

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Ly-49 receptor expression and functional analysis in multiple mouse strains

Cited by 49 publications

References 30 publications

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

Ly-49P Activates NK-Mediated Lysis by Recognizing H-2Dd 1

Complete elucidation of a minimal class I MHC natural killer cell receptor haplotype

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