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NK cells and trophoblasts: partners in pregnancy.

Parham P - J. Exp. Med. (2004)

Bottom Line: Elements of immunity were incorporated, giving pregnancy a mildly inflammatory character.Formation of the placenta, the organ that feeds the fetus, involves a cooperation between maternal natural killer (NK) cells and fetal trophoblast cells that remodels the blood supply.Recent research reveals that this process and human reproductive success are influenced by polymorphic HLA-C ligands and their killer cell immunoglobulin-like receptors (KIR).

View Article: PubMed Central - PubMed

Affiliation: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305-5126, USA. peropa@stanford.edu.

ABSTRACT
In placental mammals, viviparity--the production of living young within the mother's body--evolved under the auspices of the immune system. Elements of immunity were incorporated, giving pregnancy a mildly inflammatory character. Formation of the placenta, the organ that feeds the fetus, involves a cooperation between maternal natural killer (NK) cells and fetal trophoblast cells that remodels the blood supply. Recent research reveals that this process and human reproductive success are influenced by polymorphic HLA-C ligands and their killer cell immunoglobulin-like receptors (KIR).

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Preeclampsia is associated with uterine NK cells of KIR genotype AA and the presence of HLA-C2 on the surface of extravillous trophoblast cells. An extravillous trophoblast (EVT) is shown interacting with a maternal uterine NK cell. EVT are the only trophoblast cells that express MHC class I. The HLA-C2 molecule is shown interacting with its cognate inhibitory receptor KIR2DL1. The inhibition due to this ligand–receptor interaction favors preeclampsia in the absence of compensating activating KIR. The functional KIR genes of a group A haplotype are shown in order below the NK cell. The KIR nomenclature give the number of a receptor's extracellular domains (2D or 3D) the length of the cytoplasmic tail (long or short) and a final number distinguishing receptors with similar structure. Long-tailed KIR inhibit and short-tailed KIR activate, except KIR2DL4 which does both. HLA-C2 refers to any one of the HLA-C allotypes that has lysine at position 80. Many other ligand–receptor pairs that contribute to the cell–cell interaction are not depicted.
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fig2: Preeclampsia is associated with uterine NK cells of KIR genotype AA and the presence of HLA-C2 on the surface of extravillous trophoblast cells. An extravillous trophoblast (EVT) is shown interacting with a maternal uterine NK cell. EVT are the only trophoblast cells that express MHC class I. The HLA-C2 molecule is shown interacting with its cognate inhibitory receptor KIR2DL1. The inhibition due to this ligand–receptor interaction favors preeclampsia in the absence of compensating activating KIR. The functional KIR genes of a group A haplotype are shown in order below the NK cell. The KIR nomenclature give the number of a receptor's extracellular domains (2D or 3D) the length of the cytoplasmic tail (long or short) and a final number distinguishing receptors with similar structure. Long-tailed KIR inhibit and short-tailed KIR activate, except KIR2DL4 which does both. HLA-C2 refers to any one of the HLA-C allotypes that has lysine at position 80. Many other ligand–receptor pairs that contribute to the cell–cell interaction are not depicted.

Mentions: HLA-C allotypes form two groups according to KIR specificity and the residue present at position 80 in the amino-acid sequence (28). The C1 group allotypes are ligands for the inhibitory KIR2DL2 and KIR2DL3 and have asparagine at position 80; the C2 group allotypes are ligands for the inhibitory KIR2DL1 and the activating KIR2DS1 and have lysine at position 80. Of the two, C2 is a stronger ligand than C1 (29). Hiby et al. found that the increased prevalence of preeclampsia in AA KIR women was entirely due to pregnancies where the fetus genotype is either homozygous C2 or heterozygous C1C2. Thus, it is the combination of maternal AA KIR genotype and fetal C2 genotype which most frequently leads to preeclampsia (Fig. 2) (26).


NK cells and trophoblasts: partners in pregnancy.

Parham P - J. Exp. Med. (2004)

Preeclampsia is associated with uterine NK cells of KIR genotype AA and the presence of HLA-C2 on the surface of extravillous trophoblast cells. An extravillous trophoblast (EVT) is shown interacting with a maternal uterine NK cell. EVT are the only trophoblast cells that express MHC class I. The HLA-C2 molecule is shown interacting with its cognate inhibitory receptor KIR2DL1. The inhibition due to this ligand–receptor interaction favors preeclampsia in the absence of compensating activating KIR. The functional KIR genes of a group A haplotype are shown in order below the NK cell. The KIR nomenclature give the number of a receptor's extracellular domains (2D or 3D) the length of the cytoplasmic tail (long or short) and a final number distinguishing receptors with similar structure. Long-tailed KIR inhibit and short-tailed KIR activate, except KIR2DL4 which does both. HLA-C2 refers to any one of the HLA-C allotypes that has lysine at position 80. Many other ligand–receptor pairs that contribute to the cell–cell interaction are not depicted.
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Related In: Results  -  Collection

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fig2: Preeclampsia is associated with uterine NK cells of KIR genotype AA and the presence of HLA-C2 on the surface of extravillous trophoblast cells. An extravillous trophoblast (EVT) is shown interacting with a maternal uterine NK cell. EVT are the only trophoblast cells that express MHC class I. The HLA-C2 molecule is shown interacting with its cognate inhibitory receptor KIR2DL1. The inhibition due to this ligand–receptor interaction favors preeclampsia in the absence of compensating activating KIR. The functional KIR genes of a group A haplotype are shown in order below the NK cell. The KIR nomenclature give the number of a receptor's extracellular domains (2D or 3D) the length of the cytoplasmic tail (long or short) and a final number distinguishing receptors with similar structure. Long-tailed KIR inhibit and short-tailed KIR activate, except KIR2DL4 which does both. HLA-C2 refers to any one of the HLA-C allotypes that has lysine at position 80. Many other ligand–receptor pairs that contribute to the cell–cell interaction are not depicted.
Mentions: HLA-C allotypes form two groups according to KIR specificity and the residue present at position 80 in the amino-acid sequence (28). The C1 group allotypes are ligands for the inhibitory KIR2DL2 and KIR2DL3 and have asparagine at position 80; the C2 group allotypes are ligands for the inhibitory KIR2DL1 and the activating KIR2DS1 and have lysine at position 80. Of the two, C2 is a stronger ligand than C1 (29). Hiby et al. found that the increased prevalence of preeclampsia in AA KIR women was entirely due to pregnancies where the fetus genotype is either homozygous C2 or heterozygous C1C2. Thus, it is the combination of maternal AA KIR genotype and fetal C2 genotype which most frequently leads to preeclampsia (Fig. 2) (26).

Bottom Line: Elements of immunity were incorporated, giving pregnancy a mildly inflammatory character.Formation of the placenta, the organ that feeds the fetus, involves a cooperation between maternal natural killer (NK) cells and fetal trophoblast cells that remodels the blood supply.Recent research reveals that this process and human reproductive success are influenced by polymorphic HLA-C ligands and their killer cell immunoglobulin-like receptors (KIR).

View Article: PubMed Central - PubMed

Affiliation: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305-5126, USA. peropa@stanford.edu.

ABSTRACT
In placental mammals, viviparity--the production of living young within the mother's body--evolved under the auspices of the immune system. Elements of immunity were incorporated, giving pregnancy a mildly inflammatory character. Formation of the placenta, the organ that feeds the fetus, involves a cooperation between maternal natural killer (NK) cells and fetal trophoblast cells that remodels the blood supply. Recent research reveals that this process and human reproductive success are influenced by polymorphic HLA-C ligands and their killer cell immunoglobulin-like receptors (KIR).

Show MeSH
Related in: MedlinePlus