HLA-E is expressed on trophoblast and interacts with CD94 / NKG2 receptors on decidual NK cells

King, Ashley; Allan, David; Bowen, Mark E.; Powis, Simon J.; Joseph, Sarah; Verma, Sanjay; Hiby, Susan E.; McMichael, Andrew J.; Loke, Y.W.; Braud, Véronique M.

doi:10.1002/1521-4141(200006)30:6<1623::aid-immu1623>3.0.co;2-m

Cited by 372 publications

(219 citation statements)

References 45 publications

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“…EVTs have been shown to express the, non-classical, class I HLA-E protein (Wei & Orr 1990, King et al 2000, Ishitani et al 2003. HLA-E may also be perceived as a 'self' signal by maternal NK cells expressing the inhibitory receptor CD94/NKG2A, thus collaborating with HLA-G to prevent cytotoxicity (King et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Comparison of the expression of human leukocyte antigen (HLA)-G and HLA-E in women with normal pregnancy and those with recurrent miscarriage

Bhalla¹,

Stone²,

Liddell³

et al. 2006

Reproduction

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Recurrent miscarriage affects 1% of all couples attempting pregnancy. Immunological factors are postulated to play a role in the aetiology of recurrent miscarriage because the fetus and placenta are immunologically different from the mother. In particular, altered expression of the, non-classical, class I histocompatibility leukocyte antigen (HLA) molecules has been postulated to play a role in the aetiology of recurrent miscarriage as the fetus and placenta are semi-allogenic to the mother. This study was conducted to examine whether altered expression of the non-classical class I HLA molecules, HLA-G and HLA-E, by cells at the maternofetal interface could play a role in the aetiology of recurrent miscarriage. First-trimester placental and decidual biopsies were obtained from 45 women with recurrent miscarriage and 17 gestation-matched normal controls. These biopsies were screened by immunohistochemistry for HLA-G and HLA-E and isotype-matched control antibodies. Staining was analysed by light microscopy and digital image analysis. In both recurrent miscarriage and normal pregnancy, HLA-G was localised to the extravillous trophoblast. There was no difference in the pattern of HLA-G expression between women with recurrent miscarriage and those with normal pregnancies. HLA-E was localised to the syncytiotrophoblast, villous mesenchymal cells, extravillous trophoblast and several decidual cell types, but staining for HLA-E appeared to be confined primarily to the cytoplasm. There was no difference in the pattern of HLA-E expression between women with recurrent miscarriage and those with normal pregnancies.

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Section: Discussionmentioning

confidence: 99%

Comparison of the expression of human leukocyte antigen (HLA)-G and HLA-E in women with normal pregnancy and those with recurrent miscarriage

Bhalla¹,

Stone²,

Liddell³

et al. 2006

Reproduction

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“…A further major difficulty has been the lack of any reproducible and reliable in vitro model systems to study human trophoblast function in vitro. Nonetheless, uNK cells can be isolated and, despite their name, are poorly cytotoxic [40,41]. The input NK cells receive from KIR is either activating or inhibitory, and NK function is a result of integrating this information and responding accordingly.…”

Section: Functions Of Uterine Natural Killer Cells During Placentationmentioning

confidence: 99%

The role of the maternal immune system in the regulation of human birthweight

Moffett

Hiby

Sharkey

2015

Phil. Trans. R. Soc. B

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Human birthweight is subject to stabilizing selection. Large babies are at risk of obstetric complications such as obstructed labour, which endangers both mother and child. Small babies are also at risk with reduced survival. Fetal growth requires remodelling of maternal spiral arteries to provide an adequate maternal blood supply to the placenta. This arterial transformation is achieved by placental trophoblast cells, which invade into the uterine wall. Underinvasion is associated with fetal growth restriction; but if invasion is excessive large babies can result. A growing body of evidence suggests that this process is controlled by interactions between killer-cell immunoglobulin-like receptors (KIRs) expressed on maternal uterine natural killer cells (uNK) and their corresponding human leukocyte antigen-C (HLA-C) ligands on invading trophoblast. Mothers with the KIR AA genotype and a fetus with a paternal HLA-C2 allele tend to have small babies, because this combination inhibits cytokine secretion by uNK. Mothers with the activating KIR2DS1 gene and an HLA-C2 fetus are more likely to have large babies. When KIR2DS1 binds to HLA-C2 this increases secretion of cytokines that enhance trophoblast invasion. We conclude that specific combinations of the highly polymorphic gene systems, KIR and HLA-C, contribute to successful reproduction by maintaining birthweight between two extremes.

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“…Like CD16 Ϫ pNK cells, dNK cells lack CD16, express high levels of CD94/NKG2A receptors (6), and show low cytotoxicity against NK cell targets (7). However, many dNK cells possess KIR and large quantities of cytolytic granules, in this way resembling CD16 ϩ pNK cells (1,8).…”

mentioning

confidence: 99%

TGFβ promotes conversion of CD16⁺peripheral blood NK cells into CD16⁻NK cells with similarities to decidual NK cells

Keskin

Allan

Rybalov

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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HLA-E is expressed on trophoblast and interacts with CD94 / NKG2 receptors on decidual NK cells

Cited by 372 publications

References 45 publications

Comparison of the expression of human leukocyte antigen (HLA)-G and HLA-E in women with normal pregnancy and those with recurrent miscarriage

Comparison of the expression of human leukocyte antigen (HLA)-G and HLA-E in women with normal pregnancy and those with recurrent miscarriage

The role of the maternal immune system in the regulation of human birthweight

TGFβ promotes conversion of CD16⁺peripheral blood NK cells into CD16⁻NK cells with similarities to decidual NK cells

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HLA-E is expressed on trophoblast and interacts with CD94 / NKG2 receptors on decidual NK cells

Cited by 372 publications

References 45 publications

Comparison of the expression of human leukocyte antigen (HLA)-G and HLA-E in women with normal pregnancy and those with recurrent miscarriage

Comparison of the expression of human leukocyte antigen (HLA)-G and HLA-E in women with normal pregnancy and those with recurrent miscarriage

The role of the maternal immune system in the regulation of human birthweight

TGFβ promotes conversion of CD16+peripheral blood NK cells into CD16−NK cells with similarities to decidual NK cells

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TGFβ promotes conversion of CD16⁺peripheral blood NK cells into CD16⁻NK cells with similarities to decidual NK cells