Evidence for high bi-allelic expression of activating Ly49 receptors

Rouhi, A. Maureen; Lai, C. Benjamin; Cheng, Tammy P.; Takei, Fumio; Yokoyama, Wayne M.; Mager, Dixie L.

doi:10.1093/nar/gkp592

Cited by 19 publications

(19 citation statements)

References 52 publications

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“… reported that the co‐expression of Ly49D and Ly49H is non‐stochastic. These two molecules are the only activating Ly49 receptors found in the B6 genome, which is interesting in relation to data suggesting that the non‐stochastic regulation of the activating Ly49 receptors might be due to a distinct mode of transcriptional regulation compared to inhibitory receptors .…”

Section: The Nk Cell Inhibitory Receptor Repertoirementioning

confidence: 59%

Selection, tuning, and adaptation in mouse NK cell education

Kadri

Thanh

Höglund

2015

Immunological Reviews

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Natural killer (NK) cells recognize transformed cells with an array of germline-encoded inhibitory and activating receptors. Inhibitory Ly49 receptors bind major histocompatibility complex class I (MHC-I) molecules, providing a mechanism by which NK cells maintain self-tolerance yet eliminate cells expressing reduced levels of MHC-I. Additionally, MHC-I molecules are required for NK cell education, a process in which NK cells acquire responsiveness. In this review, we discuss three facets of MHC class I-dependent education of mouse NK cells: skewing of the inhibitory receptor repertoire, induction of functional responsiveness, and tuning in response to changes in MHC-I expression. We discuss prevailing models for education such as licensing and disarming and propose a model for positive selection of 'useful' NK cell subsets. Furthermore, we argue that both repertoire skewing and functional NK cell education may be altered in mature NK cells subject to changes in MHC-I input and suggest that this process may provide increased dynamics to the NK cell system.

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Section: The Nk Cell Inhibitory Receptor Repertoirementioning

confidence: 59%

Selection, tuning, and adaptation in mouse NK cell education

Kadri

Thanh

Höglund

2015

Immunological Reviews

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“…This reduced expression of Ly49D might be due to interactions with H-2D d in the F1. The percentages of Ly49D ϩ and Ly49H ϩ NK cells in the F1 mice were not exactly half of B6, suggesting that these receptors are expressed in a biallelic manner on at least some NK cells in the F1 mice 25 (Table 1). In addition, in these F1 mice, a higher percentage of Ly49D ϩ NK cells coexpressed more Ly49G2 and lower amounts of Ly49C/I than the Ly49D Ϫ NK-cell subset ( Figure 1B).…”

Section: Nk Cells In Cb6f1 Micementioning

confidence: 99%

The requirement for NKG2D in NK cell–mediated rejection of parental bone marrow grafts is determined by MHC class I expressed by the graft recipient

Beilke

Benjamin

Lanier

2010

Blood

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“…Based on studies of the expression of Ly49A, C, and G by individual NK cells or clones from F1 mice (36)(37)(38)(39)(40), it is generally believed that the expression of Ly49 receptors is controlled by a probabilistic mechanism in which not only each gene but also each allele of each gene is expressed independently, resulting in a partially monoallelic pattern of expression. However, whether this model applies to all Ly49 receptors is unclear, and evidence has recently been presented that Ly49H is expressed in a normal codominant manner (41). In the case of Ly49E, the limited allelic variation of Ly49E has until now precluded a determination of its pattern of expression.…”

Section: Discussionmentioning

confidence: 99%

Mice Lacking Ly49E Show Normal NK Cell Development and Provide Evidence for Probabilistic Expression of Ly49E in NK Cells and T Cells

Aust

Gays

Hussain

et al. 2011

The Journal of Immunology

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Ly49E is an unusual member of the Ly49 family that is expressed on fetal NK cells, epithelial T cells, and NKT cells, but not on resting adult NK cells. Ly49Ebgeo/bgeo mice in which the Ly49E gene was disrupted by inserting a β-geo transgene were healthy, fertile, and had normal numbers of NK and T cells in all organs examined. Their NK cells displayed normal expression of Ly49 and other NK cell receptors, killed tumor and MHC class I-deficient cells efficiently, and produced normal levels of IFN-γ. In heterozygous Ly49E+/bgeo mice, the proportion of epidermal T cells, NKT cells, and IL-2–activated NK cells that expressed Ly49E was about half that found in wild-type mice. Surprisingly, although splenic T cells rarely expressed Ly49E, IL-2–activated splenic T cells from Ly49Ebgeo/bgeo mice were as resistant to growth in G418 as NK cells and expressed similar levels of β-geo transcripts, suggesting that disruption of the Ly49E locus had increased its expression in these cells to the same level as that in NK cells. Importantly, however, the proportion of G418-resistant heterozygous Ly49E+/bgeo cells that expressed Ly49E from the wild-type allele was similar to that observed in control cells. Collectively, these findings demonstrate that Ly49E is not required for the development or homeostasis of NK and T cell populations or for the acquisition of functional competence in NK cells and provide compelling evidence that Ly49E is expressed in a probabilistic manner in adult NK cells and T cells.

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Evidence for high bi-allelic expression of activating Ly49 receptors

Cited by 19 publications

References 52 publications

Selection, tuning, and adaptation in mouse NK cell education

Selection, tuning, and adaptation in mouse NK cell education

The requirement for NKG2D in NK cell–mediated rejection of parental bone marrow grafts is determined by MHC class I expressed by the graft recipient

Mice Lacking Ly49E Show Normal NK Cell Development and Provide Evidence for Probabilistic Expression of Ly49E in NK Cells and T Cells

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