scholarly journals High-Resolution Analysis Identifies High Frequency of KIR-A Haplotypes and Inhibitory Interactions of KIR With HLA Class I in Zhejiang Han

2021 ◽  
Vol 12 ◽  
Author(s):  
Sudan Tao ◽  
Yanmin He ◽  
Katherine M. Kichula ◽  
Jielin Wang ◽  
Ji He ◽  
...  
Keyword(s):  
High Resolution ◽  
High Frequency ◽  
Killer Cell ◽  
Hla Class I ◽  
Class I ◽  
Gene Copy ◽  
Human Populations ◽  
Telomeric Region ◽  
Cell Functions ◽  
Hla Class I Molecules

Killer cell immunoglobulin-like receptors (KIR) interact with human leukocyte antigen (HLA) class I molecules, modulating critical NK cell functions in the maintenance of human health. Characterizing the distribution and characteristics of KIR and HLA allotype diversity across defined human populations is thus essential for understanding the multiple associations with disease, and for directing therapies. In this study of 176 Zhejiang Han individuals from Southeastern China, we describe diversity of the highly polymorphic KIR and HLA class I genes at high resolution. KIR-A haplotypes, which carry four inhibitory receptors specific for HLA-A, B or C, are known to associate with protection from infection and some cancers. We show the Chinese Southern Han from Zhejiang are characterized by a high frequency of KIR-A haplotypes and a high frequency of C1 KIR ligands. Accordingly, interactions of inhibitory KIR2DL3 with C1+HLA are more frequent in Zhejiang Han than populations outside East Asia. Zhejiang Han exhibit greater diversity of inhibitory than activating KIR, with three-domain inhibitory KIR exhibiting the greatest degree of polymorphism. As distinguished by gene copy number and allele content, 54 centromeric and 37 telomeric haplotypes were observed. We observed 6% of the population to have KIR haplotypes containing large-scale duplications or deletions that include complete genes. A unique truncated haplotype containing only KIR2DL4 in the telomeric region was also identified. An additional feature is the high frequency of HLA-B*46:01, which may have arisen due to selection pressure from infectious disease. This study will provide further insight into the role of KIR and HLA polymorphism in disease susceptibility of Zhejiang Chinese.

scholarly journals Adaptive Admixture of HLA class I Allotypes Enhanced Genetically Determined Strength of Natural Killer Cells in East Asians

2021 ◽  
Author(s):  
Zhihui Deng ◽  
Jianxin Zhen ◽  
Genelle F Harrison ◽  
Guobin Zhang ◽  
Rui Chen ◽  
...  
Keyword(s):  
Natural Killer ◽  
High Frequency ◽  
Nk Cell ◽  
Killer Cell ◽  
Hla Class I ◽  
Class I ◽  
Telomeric Region ◽  
East Asians ◽  
Cell Functions ◽  
Specific Receptors

Abstract Human natural killer (NK) cells are essential for controlling infection, cancer and fetal development. NK cell functions are modulated by interactions between polymorphic inhibitory killer cell immunoglobulin-like receptors (KIR) and polymorphic HLA-A, -B and -C ligands expressed on tissue cells. All HLA-C alleles encode a KIR ligand and contribute to reproduction and immunity. In contrast, only some HLA-A and -B alleles encode KIR ligands and they focus on immunity. By high-resolution analysis of KIR and HLA-A, -B and -C genes, we show that the Chinese Southern Han are significantly enriched for interactions between inhibitory KIR and HLA-A and -B. This enrichment has had substantial input through population admixture with neighboring populations, who contributed HLA class I haplotypes expressing the KIR ligands B*46:01 and B*58:01, which subsequently rose to high frequency by natural selection. Consequently, over 80% of Southern Han HLA haplotypes encode more than one KIR ligand. Complementing the high number of KIR ligands, the Chinese Southern Han KIR locus combines a high frequency of genes expressing potent inhibitory KIR, with a low frequency of those expressing activating KIR. The Southern Han centromeric KIR region encodes strong, conserved, inhibitory HLA-C specific receptors, and the telomeric region provides a high number and diversity of inhibitory HLA-A and -B specific receptors. In all these characteristics, the Chinese Southern Han represent other East Asians, whose NK cell repertoires are thus enhanced in quantity, diversity and effector strength, likely augmenting resistance to endemic viral infections.

scholarly journals Genetically Determined Strength of Natural Killer Cells is Enhanced by Adaptive HLA class I Admixture in East Asians

2020 ◽  
Author(s):  
Zhihui Deng ◽  
Jianxin Zhen ◽  
Genelle F. Harrison ◽  
Guobin Zhang ◽  
Rui Chen ◽  
...  
Keyword(s):  
Natural Selection ◽  
Natural Killer ◽  
High Frequency ◽  
Nk Cell ◽  
Hla Class I ◽  
Class I ◽  
Telomeric Region ◽  
East Asians ◽  
Cell Functions ◽  
Specific Receptors

AbstractHuman natural killer (NK) cells are essential for controlling infection, cancer and fetal development. NK cell functions are modulated by interactions between polymorphic inhibitory killer cell immunoglobulin-like receptors (KIR) and polymorphic HLA-A, -B and -C ligands expressed on tissue cells. All HLA-C alleles encode a KIR ligand and contribute to reproduction and immunity. In contrast, only some HLA-A and -B alleles encode KIR ligands and they focus on immunity. By high-resolution analysis of KIR and HLA-A, -B and -C genes, we show that the Chinese Southern Han are significantly enriched for interactions between inhibitory KIR and HLA-A and -B. This enrichment has had substantial input through population admixture with neighboring populations, who contributed HLA class I haplotypes expressing the KIR ligands B*46:01 and B*58:01, which subsequently rose to high frequency by natural selection. Consequently, over 80% of Southern Han HLA haplotypes encode more than one KIR ligand. Complementing the high number of KIR ligands, the Chinese Southern Han KIR locus combines a high frequency of genes expressing potent inhibitory KIR, with a low frequency of those expressing activating KIR. The Southern Han centromeric KIR region encodes strong, conserved, inhibitory HLA-C specific receptors, and the telomeric region provides a high number and diversity of inhibitory HLA-A and -B specific receptors. In all these characteristics, the Southern Han represent other East Asians, whose NK cell repertoires are thus enhanced in quantity, diversity and effector strength, likely through natural selection for resistance to endemic viral infections.

scholarly journals Human natural killer cell receptors for HLA-class I molecules. Evidence that the Kp43 (CD94) molecule functions as receptor for HLA-B alleles.

1994 ◽  
Vol 180 (2) ◽  
pp. 545-555 ◽  
Author(s):  
A Moretta ◽  
M Vitale ◽  
S Sivori ◽  
C Bottino ◽  
L Morelli ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Killer Cell ◽  
Hla Class I ◽  
Cytolytic Activity ◽  
Class I ◽  
Target Cells ◽  
Human Natural Killer Cell ◽  
Ligand Interaction ◽  
Hla Class I Molecules

GL183 or EB6 (p58) molecules have been shown to function as receptors for different HLA-C alleles and to deliver an inhibitory signal to natural killer (NK) cells, thus preventing lysis of target cells. In this study, we analyzed a subset of NK cells characterized by a p58-negative surface phenotype. We show that p58-negative clones, although specific for class I molecules do not recognize HLA-C alleles. In addition, by the use of appropriate target cells transfected with different HLA-class I alleles we identified HLA-B7 as the protective element recognized by a fraction of p58-negative clones. In an attempt to identify the receptor molecules expressed by HLA-B7-specific clones, monoclonal antibodies (mAbs) were selected after mice immunization with such clones. Two of these mAbs, termed XA-88 and XA-185, and their F(ab')2 fragments, were found to reconstitute lysis of B7+ target cells by B7-specific NK clones. Both mAbs were shown to be directed against the recently clustered Kp43 molecule (CD94). Thus, mAb-mediated masking of Kp43 molecules interferes with recognition of HLA-B7 and results in target cell lysis. Moreover, in a redirected killing assay, the cross-linking of Kp43 molecules mediated by the XA185 mAb strongly inhibited the cytolytic activity of HLA-B7-specific NK clones, thus mimicking the functional effect of B7 molecules. Taken together, these data strongly suggest that Kp43 molecules function as receptors for HLA-B7 and that this receptor/ligand interaction results in inhibition of the NK-mediated cytolytic activity. Indirect immunofluorescence and FACS analysis of a large number of random NK clones showed that Kp43 molecules (a) were brightly expressed on a subset of p58-negative clones, corresponding to those specific for HLA-B7; (b) displayed a medium/low fluorescence in the p58-negative clones that are not B7-specific as well as in most p58+ NK clones; and (c) were brightly expressed as in the p58+ clone ET34 (GL183-/EB6+, Cw4-specific). Functional analysis revealed that Kp43 functioned as an inhibitory receptor only in NK clones displaying bright fluorescence. These studies also indicate that some NK clones (e.g., the ET34) can coexpress two distinct receptors (p58 and Kp43) for different class I alleles (Cw4 and B7). Finally, we show that Kp43 molecules function as receptors only for some HLA-B alleles and that still undefined receptor(s) must exist for other HLA-B alleles including B27.

The CD94 and NKG2-A C-type lectins covalently assemble to form a natural killer cell inhibitory receptor for HLA class I molecules

1997 ◽  
Vol 27 (2) ◽  
pp. 563-567 ◽  
Author(s):  
Marta Carretero ◽  
Claudia Cantoni ◽  
Teresa Bellón ◽  
Cristina Bottino ◽  
Roberto Biassoni ◽  
...  
Keyword(s):  
Natural Killer Cell ◽  
Natural Killer ◽  
Killer Cell ◽  
Hla Class I ◽  
Class I ◽  
Inhibitory Receptor ◽  
Hla Class I Molecules ◽  
Killer Cell Inhibitory Receptor

Killer cell inhibitory receptor interactions with HLA class I molecules

1997 ◽  
Vol 52 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Neil T. Young ◽  
Mike Bunce ◽  
Peter J. Morris ◽  
Ken I. Welsh
Keyword(s):  
Killer Cell ◽  
Hla Class I ◽  
Class I ◽  
Inhibitory Receptor ◽  
Hla Class I Molecules ◽  
Receptor Interactions ◽  
Killer Cell Inhibitory Receptor

scholarly journals A Human Histocompatibility Leukocyte Antigen (HLA)-G–specific Receptor Expressed on All Natural Killer Cells

1999 ◽  
Vol 189 (7) ◽  
pp. 1093-1100 ◽  
Author(s):  
Sumati Rajagopalan ◽  
Eric O. Long
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Killer Cell ◽  
Hla Class I ◽  
Class I ◽  
Target Cells ◽  
Trophoblast Cells ◽  
Leukocyte Antigen ◽  
Hla Class I Molecules ◽  
Decidual Cells

Human natural killer (NK) cells express several killer cell immunoglobulin (Ig)-like receptors (KIRs) that inhibit their cytotoxicity upon recognition of human histocompatibility leukocyte antigen (HLA) class I molecules on target cells. Additional members of the KIR family, including some that deliver activation signals, have unknown ligand specificity and function. One such KIR, denoted KIR2DL4, is structurally divergent from other KIRs in the configuration of its two extracellular Ig domains and of its transmembrane and cytoplasmic domains. Here we show that recombinant soluble KIR2DL4 binds to cells expressing HLA-G but not to cells expressing other HLA class I molecules. Unlike other HLA class I–specific KIRs, which are clonally distributed on NK cells, KIR2DL4 is expressed at the surface of all NK cells. Furthermore, functional transfer of KIR2DL4 into the cell line NK-92 resulted in inhibition of lysis of target cells that express HLA-G, but not target cells that express other class I molecules including HLA-E. Therefore, given that HLA-G expression is restricted to fetal trophoblast cells, KIR2DL4 may provide important signals to maternal NK decidual cells that interact with trophoblast cells at the maternal–fetal interface during pregnancy.

scholarly journals Natural killer cell licensing after double cord blood transplantation is driven by the self-HLA class I molecules from the dominant cord blood

Haematologica ◽  
2016 ◽  
Vol 101 (5) ◽  
pp. e209-e212 ◽  
Author(s):  
N. Guillaume ◽  
P. Loiseau ◽  
K. Gagne ◽  
H. Moins-Teissserenc ◽  
J.-M. Cayuela ◽  
...  
Keyword(s):  
Natural Killer Cell ◽  
Cord Blood ◽  
Natural Killer ◽  
Cord Blood Transplantation ◽  
Killer Cell ◽  
Hla Class I ◽  
The Self ◽  
Class I ◽  
Blood Transplantation ◽  
Hla Class I Molecules

scholarly journals The Interaction of LILRB2 with HLA-B is Associated with Psoriasis Susceptibility

2019 ◽  
Author(s):  
Rebecca L. Yanovsky ◽  
Haoyan Chen ◽  
Stephen Leslie ◽  
Mary Carrington ◽  
Wilson Liao
Keyword(s):  
Genome Wide Association Study ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Antigen Presenting Cells ◽  
Hla Class I ◽  
Class I ◽  
Hla Class I Molecules ◽  
Genome Wide ◽  
Related Group ◽  
Antigen Presenting

ABSTRACTGenetic variation within the major histocompatibility complex (MHC) class I is a well-known risk factor for psoriasis. While the mechanisms behind this variation are still being fully elucidated, human leukocyte antigen (HLA) presentation of auto-antigens as well as the interaction of HLA-B with killer cell immunoglobulin-like receptors (KIRs) have been shown to contribute to psoriasis susceptibility. Here we demonstrate that the interaction of HLA class I molecules with leukocyte immunoglobulin-like receptors (LILR), a related group of immunomodulatory receptors primarily found on antigen presenting cells, also contributes to psoriasis susceptibility. We used previously characterized binding capacities of HLA-A, HLA-B, and HLA-C allotypes to two inhibitory LILRs, LILRB1 and LILRB2, to investigate the effect of LILRB1/2 binding in two large genome wide association study cohorts of psoriasis patients and controls (N = 10,069). We found that the strength of binding of LILRB2 to HLA-B was inversely associated with psoriasis risk (p = 2.34E-09, OR [95% CI], 0.41 [0.30−0.55]) independent of individual class I or II allelic effects. We thus propose that weak binding of inhibitory LILRB2 to HLA-B may play a role in patient susceptibility to psoriasis via increased activity of antigen presenting cells.

scholarly journals Recognition of Human Histocompatibility Leukocyte Antigen (HLA)-E Complexed with HLA Class I Signal Sequence–derived Peptides by CD94/NKG2 Confers Protection from Natural Killer Cell–mediated Lysis

1998 ◽  
Vol 187 (5) ◽  
pp. 813-818 ◽  
Author(s):  
Francisco Borrego ◽  
Matthias Ulbrecht ◽  
Elisabeth H. Weiss ◽  
John E. Coligan ◽  
Andrew G. Brooks
Keyword(s):  
Cell Surface ◽  
Natural Killer ◽  
Signal Sequence ◽  
Killer Cell ◽  
Hla Class I ◽  
Class I ◽  
Target Cells ◽  
Leukocyte Antigen ◽  
Hla Class I Molecules ◽  
Sequence Position

Human histocompatibility leukocyte antigen (HLA)-E is a nonclassical HLA class I molecule, the gene for which is transcribed in most tissues. It has recently been reported that this molecule binds peptides derived from the signal sequence of HLA class I proteins; however, no function for HLA-E has yet been described. We show that natural killer (NK) cells can recognize target cells expressing HLA-E molecules on the cell surface and this interaction results in inhibition of the lytic process. Furthermore, HLA-E recognition is mediated primarily through the CD94/NKG2-A heterodimer, as CD94-specific, but not killer cell inhibitory receptor (KIR)–specific mAbs block HLA-E–mediated protection of target cells. Cell surface HLA-E could be increased by incubation with synthetic peptides corresponding to residues 3–11 from the signal sequences of a number of HLA class I molecules; however, only peptides which contained a Met at position 2 were capable of conferring resistance to NK-mediated lysis, whereas those having Thr at position 2 had no effect. Interestingly, HLA class I molecules previously correlated with CD94/NKG2 recognition all have Met at residue 4 of the signal sequence (position 2 of the HLA-E binding peptide), whereas those which have been reported not to interact with CD94/NKG2 have Thr at this position. Thus, these data show a function for HLA-E and suggest an alternative explanation for the apparent broad reactivity of CD94/NKG2 with HLA class I molecules; that CD94/NKG2 interacts with HLA-E complexed with signal sequence peptides derived from “protective” HLA class I alleles rather than directly interacting with classical HLA class I proteins.

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