α1 / α2 domains of H-2Dd, but not H-2Ld, induce "missing self" reactivity in vivo – No effect of H-2Ld on protection against NK cells expressing the inhibitory receptor Ly49G2

Johansson, Maria H.; Höglund, Elin; Nakamura, Mary C.; Ryan, James C.

doi:10.1002/(sici)1521-4141(199812)28:12<4198::aid-immu4198>3.3.co;2-0

Cited by 11 publications

(17 citation statements)

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“…This is consistent with studies of Ly49C in which H-2 d expression of the host had no influence on the cell surface levels of this receptor [28]; host expression of an MHC class I ligand usually leads to reduced expression of the corresponding receptors on NK cells [29]. However, the evidence for protection as well as modulated expression of Ly49G2 in response to H-2D d is more convincing [17,18].…”

Section: Soluble H-2d D Molecules Bind Ly49asupporting

confidence: 86%

“…This makes the analysis of receptor specificity difficult, especially in cellular adhesion or functional killing assays that depend on a combination of receptors and ligands as well as other properties of the NK cells and target cells studied. On the basis of such assays, Ly49A has been reported to bind to H-2D d , H-2D k and H-2D p [7,15,16], Ly49G2 to H-2D d and H-2L d [17,18] and Ly49C to H-2K b , H-2K d , H-2D d , H-2D b and H-2 s encoded class I molecules [19,20].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2000

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Section: Soluble H-2d D Molecules Bind Ly49asupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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

et al. 2000

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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: 44%

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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“…The Ly-49 multigene family encodes a complex and polymorphic family of NK cell surface receptors, at least some of which recognize class I MHC molecules and send an inhibitory signal that represses the lytic activity of NK cells (28,33). The lytic activity of the Ly-49G2 ϩ subset of NK cells is inhibited by target cells expressing H-2D d and or H-2L d (32), although inhibition by H-2L d has recently come into question (38). As a consequence of this class I-mediated inhibitory activity, Ly-49G2 ϩ LAK cells from C57BL/6 mice are incapable of lysing the LAK-sensitive target P815, which is H-2D d (32).…”

Section: Figurementioning

confidence: 99%

Differentiation of Murine NK Cells into Distinct Subsets Based on Variable Expression of the IL-12Rβ2 Subunit

Chakir

Camilucci

Filion

et al. 2000

The Journal of Immunology

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The cytokine IL-12 manifests its biological activity via interaction with a heterodimeric receptor (IL-12R) present on activated T and NK cells. The cDNAs for two IL-12R subunits have been cloned from human and mouse and designated IL-12Rβ1 and IL-12Rβ2. The expression of IL-12Rβ2 on T cells is influenced by cytokines, particularly IL-4, IL-12, and IFN-γ; however, little is known regarding regulation of IL-12R expression on NK cells. In this study we show that murine NK cells differentiate into IL-12Rβ2low and IL-12Rβ2high subsets after in vitro stimulation with IL-2 in the absence of exogenous polarizing cytokines. Subset development occurs gradually as NK cells expand in vitro and is generally complete by 8–12 days of culture. Once established, IL-12Rβ2low and IL-12Rβ2high subsets are highly stable in vitro and can be maintained for at least 20 days after FACS sorting. Formation of these NK subsets appears to be strain independent. Flow cytometric analyses demonstrate that both subsets express a number of NK-associated markers, including NK1.1, DX-5, Ly-49A, and Ly-49C, but that the Ly-49G2 class I inhibitory receptor is expressed predominantly on the IL-12Rβ2high population. Both IL-12Rβ2low and IL-12Rβ2high NK cells respond to exogenous IL-12 by rapid production of high levels of IFN-γ and increased lytic activity against NK-sensitive YAC-1 target cells. Analyses of cytokine gene expression by RNase protection assay indicated that similar to the recently described human NK1 subset, both IL-12Rβ2high and IL-12Rβ2low murine NK subsets expressed high levels of IFN-γ, whereas neither subset expressed mRNA for the NK2-associated cytokines IL-5 and IL-13.

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α1 / α2 domains of H-2Dd, but not H-2Ld, induce "missing self" reactivity in vivo – No effect of H-2Ld on protection against NK cells expressing the inhibitory receptor Ly49G2

Cited by 11 publications

References 0 publications

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

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

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

Differentiation of Murine NK Cells into Distinct Subsets Based on Variable Expression of the IL-12Rβ2 Subunit

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