scholarly journals Structural plasticity of KIR2DL2 and KIR2DL3 enables altered docking geometries atop HLA-C

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shoeib Moradi ◽  
Sanda Stankovic ◽  
Geraldine M. O’Connor ◽  
Phillip Pymm ◽  
Bruce J. MacLachlan ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
Human Leukocyte Antigen ◽  
Nk Cells ◽  
Natural Killer ◽  
Crystal Structures ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Functional Differences ◽  
Molecular Bases

AbstractThe closely related inhibitory killer-cell immunoglobulin-like receptors (KIR), KIR2DL2 and KIR2DL3, regulate the activation of natural killer cells (NK) by interacting with the human leukocyte antigen-C1 (HLA-C1) group of molecules. KIR2DL2, KIR2DL3 and HLA-C1 are highly polymorphic, with this variation being associated with differences in the onset and progression of some human diseases. However, the molecular bases underlying these associations remain unresolved. Here, we determined the crystal structures of KIR2DL2 and KIR2DL3 in complex with HLA-C*07:02 presenting a self-epitope. KIR2DL2 differed from KIR2DL3 in docking modality over HLA-C*07:02 that correlates with variabilty of recognition of HLA-C1 allotypes. Mutagenesis assays indicated differences in the mechanism of HLA-C1 allotype recognition by KIR2DL2 and KIR2DL3. Similarly, HLA-C1 allotypes differed markedly in their capacity to inhibit activation of primary NK cells. These functional differences derive, in part, from KIR2DS2 suggesting KIR2DL2 and KIR2DL3 binding geometries combine with other factors to distinguish HLA-C1 functional recognition.

scholarly journals Killer Cell Inhibitory Receptor Recognition of Human Leukocyte Antigen (HLA) Class I Blocks Formation of a pp36/PLC-γ Signaling Complex in Human Natural Killer (NK) Cells

1996 ◽  
Vol 184 (6) ◽  
pp. 2243-2250 ◽  
Author(s):  
Nicholas M. Valiante ◽  
Joseph H. Phillips ◽  
Lewis L. Lanier ◽  
Peter Parham
Keyword(s):  
Human Leukocyte Antigen ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Class I ◽  
Cell Cytotoxicity ◽  
Leukocyte Antigen ◽  
Nk Cell Cytotoxicity

The killer cell inhibitory receptors (KIR) of human natural killer (NK) cells recognize human leukocyte antigen class I molecules and inhibit NK cell cytotoxicity through their interaction with protein tyrosine phosphatases (PTP). Here, we report that KIR recognition of class I ligands inhibits distal signaling events and ultimately NK cell cytotoxicity by blocking the association of an adaptor protein (pp36) with phospholipase C-γ in NK cells. In addition, we demonstrate that pp36 can serve as a substrate in vitro for the KIR-associated PTP, PTP-1C (also called SHP-1), and that recognition of class I partially disrupts tyrosine phosphorylation of NK cell proteins, providing evidence for KIR-induced phosphatase activity.

scholarly journals EXPRESSION OF HUMAN LEUKOCYTE ANTIGEN-E AND NATURAL KILLER CELLS IN INTRA UTERINE FETAL DEATH

2017 ◽  
Vol 53 (4) ◽  
pp. 252
Author(s):  
Sri Sulistyowati ◽  
Muhammad Anggit Nugroho ◽  
Supriyadi Hari Respati ◽  
Soetrisno Soetrisno
Keyword(s):  
Natural Killer Cells ◽  
Human Leukocyte Antigen ◽  
Nk Cells ◽  
Natural Killer ◽  
Fetal Death ◽  
Human Leukocyte ◽  
Normal Pregnancy ◽  
Mean Value ◽  
Leukocyte Antigen ◽  
The Mean

Intra Uterine Fetal Death (IUFD) is one contributor to infant mortality. Human Leukocyte Antigen-E (HLA-E) and Natural Killer Cells (NK cells) are believed to play an important role towards IUFD associated with immune maladaptation. This study aimed to determine the expression of HLA-E and NK cells on trophoblast on IUFD and normal pregnancy. The study used cross sectional approach undertaken at Department of Obstetrics and Gynecology, Dr. Moewardi Hospital, Surakarta, networking hospitals, and Anatomic Pathology Laboratory of Faculty of Medicine, Sebelas Maret University. The number of samples were 32 subjects consisting of 16 subjects with normal pregnancy and 16 subjects with IUFD. The expression of HLA-E and NK cells on trophoblast of subjects who met the inclusion and exclusion criteria were examined using immunohistochemistry method and t-test statistical analysis. The mean value of HLA-E expression in the trophoblast of IUFD group was 17.30±6.69, in normal pregnancy was 57.06±32.04, with p=0.00 (p<0.05). The mean value of NK cell expression in trophoblast in IUFD group was 78.62±36.43, in normal pregnancy was 19.87±6.43, with p=0.00 (p<0.05). This study concluded that the expression of HLA-E was lower and NK cells wass higher in IUFD compared to those in normal pregnancy.

scholarly journals The molecular basis of how buried human leukocyte antigen polymorphism modulates natural killer cell function

2020 ◽  
Vol 117 (21) ◽  
pp. 11636-11647 ◽  
Author(s):  
Philippa M. Saunders ◽  
Bruce J. MacLachlan ◽  
Phillip Pymm ◽  
Patricia T. Illing ◽  
Yuanchen Deng ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Peptide Binding ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Cell Recognition ◽  
Leukocyte Antigen ◽  
Binding Cleft

Micropolymorphisms within human leukocyte antigen (HLA) class I molecules can change the architecture of the peptide-binding cleft, leading to differences in peptide presentation and T cell recognition. The impact of such HLA variation on natural killer (NK) cell recognition remains unclear. Given the differential association of HLA-B*57:01 and HLA-B*57:03 with the control of HIV, recognition of these HLA-B57 allomorphs by the killer cell immunoglobulin-like receptor (KIR) 3DL1 was compared. Despite differing by only two polymorphic residues, both buried within the peptide-binding cleft, HLA-B*57:01 more potently inhibited NK cell activation. Direct-binding studies showed KIR3DL1 to preferentially recognize HLA-B*57:01, particularly when presenting peptides with positively charged position (P)Ω-2 residues. In HLA-B*57:01, charged PΩ-2 residues were oriented toward the peptide-binding cleft and away from KIR3DL1. In HLA-B*57:03, the charged PΩ-2 residues protruded out from the cleft and directly impacted KIR3DL1 engagement. Accordingly, KIR3DL1 recognition of HLA class I ligands is modulated by both the peptide sequence and conformation, as determined by the HLA polymorphic framework, providing a rationale for understanding differences in clinical associations.

scholarly journals Increased frequency of human leukocyte antigen–E inhibitory receptor CD94/NKG2A–expressing peritoneal natural killer cells in patients with endometriosis

2008 ◽  
Vol 89 (5) ◽  
pp. 1490-1496 ◽  
Author(s):  
Ricciarda Galandrini ◽  
Maria Grazia Porpora ◽  
Antonella Stoppacciaro ◽  
Federica Micucci ◽  
Cristina Capuano ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
Human Leukocyte Antigen ◽  
Natural Killer ◽  
Human Leukocyte ◽  
Inhibitory Receptor ◽  
Killer Cells ◽  
Leukocyte Antigen

scholarly journals The human leukocyte antigen (HLA)-C-specific "activatory" or "inhibitory" natural killer cell receptors display highly homologous extracellular domains but differ in their transmembrane and intracytoplasmic portions.

1996 ◽  
Vol 183 (2) ◽  
pp. 645-650 ◽  
Author(s):  
R Biassoni ◽  
C Cantoni ◽  
M Falco ◽  
S Verdiani ◽  
C Bottino ◽  
...  
Keyword(s):  
Amino Acid ◽  
Human Leukocyte Antigen ◽  
Natural Killer ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Receptor Activation ◽  
Leukocyte Antigen ◽  
Allele Specificity ◽  
Specific Receptors ◽  
Activation Motif

Natural killer cells express clonally distributed receptors specific for major histocompatibility complex class I molecules. The human leukocyte antigen (HLA)-C-specific receptors have been molecularly identified and cloned. They exist not only as inhibitory (p58) but also as activatory (p50) receptors. Here we show that p50 and p58 are highly homologous in their extracellular regions formed by two Ig-like domains. In contrast, major differences exist in their transmembrane and cytoplasmic portions. Whereas p 58 displays a 76-84-amino acid cytoplasmic tail containing an unusual antigen receptor activation motif, p50 is characterized by a shorter 39-amino acid tail. In addition, whereas p58 has a nonpolar transmembrane portion, p50 contains the charged amino acid Lys. These data strongly suggest that receptors with identical HLA-C allele specificity can mediate functions of opposite sign owing to their different transmembrane/cytoplasmic portions.

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