scholarly journals KIR gene content imputation from single-nucleotide polymorphisms in the Finnish population

PeerJ ◽  
2022 ◽  
Vol 10 ◽  
pp. e12692
Author(s):  
Jarmo Ritari ◽  
Kati Hyvärinen ◽  
Jukka Partanen ◽  
Satu Koskela
Keyword(s):  
Viral Infections ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Activity ◽  
Gene Copy Number ◽  
Human Leukocyte ◽  
Gene Content ◽  
Gene Copy ◽  
Nucleotide Polymorphisms ◽  
Kir Gene

The killer cell immunoglobulin-like receptor (KIR) gene cluster on chromosome 19 encodes cell surface glycoproteins that bind class I human leukocyte antigen (HLA) molecules as well as some other ligands. Through regulation of natural killer (NK) cell activity KIRs participate in tumour surveillance and clearing viral infections. KIR gene gene copy number variation associates with the outcome of transplantations and susceptibility to immune-mediated diseases. Inferring KIR gene content from genetic variant data is therefore desirable for immunogenetic analysis, particularly in the context of growing biobank genome data collections that rely on genotyping by microarray. Here we describe a stand-alone and freely available gene content imputation for 12 KIR genes. The models were trained using 807 Finnish biobank samples genotyped for 5900 KIR-region SNPs and analysed for KIR gene content with targeted sequencing. Cross-validation results demonstrate a high mean overall accuracy of 98.5% (95% CI [97.0–99.2]%) which compares favourably with previous methods including short-read sequencing based approaches.

scholarly journals KIR gene content imputation from single-nucleotide polymorphisms in the Finnish population

2021 ◽  
Author(s):  
Jarmo Ritari ◽  
Kati Hyvarinen ◽  
Jukka Partanen ◽  
Satu Koskela
Keyword(s):  
Viral Infections ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Activity ◽  
Gene Copy Number ◽  
Human Leukocyte ◽  
Gene Content ◽  
Gene Copy ◽  
Nucleotide Polymorphisms ◽  
Kir Gene

The killer cell immunoglobulin-like receptor (KIR) gene cluster on chromosome 19 encodes cell surface glycoproteins that bind class I human leukocyte antigen (HLA) molecules as well as some other ligands. Through regulation of natural killer (NK) cell activity KIRs participate in tumour surveillance and clearing viral infections. KIR gene gene copy number variation associates with the outcome of transplantations and susceptibility to immune-mediated diseases. Inferring KIR gene content from genetic variant data is therefore desirable for immunogenetic analysis, particularly in the context of growing biobank genome data collections that rely on genotyping by microarray. Here we describe a stand-alone and freely available gene content imputation for 12 KIR genes. The models were trained using 818 Finnish biobank samples genotyped for 5774 KIR-region SNPs and analysed for KIR gene content with targeted sequencing. Cross-validation results demonstrate a high mean overall accuracy of 99.2% (95% CI: 97.8-99.7%) which compares favourably with previous methods including short-read sequencing based approaches.

scholarly journals Influence of KIR gene copy number on natural killer cell education

Blood ◽  
2013 ◽  
Vol 121 (23) ◽  
pp. 4703-4707 ◽  
Author(s):  
Vivien Béziat ◽  
James A. Traherne ◽  
Lisa L. Liu ◽  
Jyothi Jayaraman ◽  
Monika Enqvist ◽  
...  
Keyword(s):  
Copy Number ◽  
Nk Cell ◽  
Killer Cell ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Linear Effect ◽  
Gene Copy Number Variation ◽  
Key Points ◽  
Number Variation ◽  
Kir Gene

Key Points KIR gene copy number variation influences NK cell education at the repertoire level due to a linear effect on KIR expression. No effect of KIR gene dose on NK cell education at the single cell level.

scholarly journals Immunosurveillance of Cancer and Viral Infections with Regard to Alterations of Human NK Cells Originating from Lifestyle and Aging

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 557
Author(s):  
Xuewen Deng ◽  
Hiroshi Terunuma ◽  
Mie Nieda
Keyword(s):  
Nk Cells ◽  
Viral Infections ◽  
Nk Cell ◽  
Healthy Lifestyle ◽  
Cell Activity ◽  
Nk Cell Activity ◽  
Effector Cells ◽  
Cell Dysfunction ◽  
Forest Bathing ◽  
Infected Cells

Natural killer (NK) cells are cytotoxic immune cells with an innate capacity for eliminating cancer cells and virus- infected cells. NK cells are critical effector cells in the immunosurveillance of cancer and viral infections. Patients with low NK cell activity or NK cell deficiencies are predisposed to increased risks of cancer and severe viral infections. However, functional alterations of human NK cells are associated with lifestyles and aging. Personal lifestyles, such as cigarette smoking, alcohol consumption, stress, obesity, and aging are correlated with NK cell dysfunction, whereas adequate sleep, moderate exercise, forest bathing, and listening to music are associated with functional healthy NK cells. Therefore, adherence to a healthy lifestyle is essential and will be favorable for immunosurveillance of cancer and viral infections with healthy NK cells.

scholarly journals Coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elham Ashouri ◽  
Karan Rajalingam ◽  
Shaghik Barani ◽  
Shirin Farjadian ◽  
Abbas Ghaderi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Cancer ◽  
Cell Function ◽  
Nk Cell ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Risk Scores ◽  
Hla Ligands ◽  
Nk Cytotoxicity

AbstractHuman leukocyte antigen (HLA) class I-specific killer-cell immunoglobulin-like receptors (KIR) regulate natural killer (NK) cell function in eliminating malignancy. Breast cancer (BC) patients exhibit reduced NK-cytotoxicity in peripheral blood. To test the hypothesis that certain KIR-HLA combinations impairing NK-cytotoxicity predispose to BC risk, we analyzed KIR and HLA polymorphisms in 162 women with BC and 278 controls. KIR-Bx genotypes increased significantly in BC than controls (83.3% vs. 71.9%, OR 1.95), and the increase was more pronounced in advanced-cancer (OR 5.3). No difference was observed with inhibitory KIR (iKIR) and HLA-ligand combinations. The activating KIR (aKIR) and HLA-ligand combinations, 2DS1 + C2 (OR 2.98) and 3DS1 + Bw4 (OR 2.6), were significantly increased in advanced-BC. All patients with advanced-cancer carrying 2DS1 + C2 or 3DS1 + Bw4 also have their iKIR counterparts 2DL1 and 3DL1, respectively. Contrarily, the 2DL1 + C2 and 3DL1 + Bw4 pairs without their aKIR counterparts are significantly higher in controls. These data suggest that NK cells expressing iKIR to the cognate HLA-ligands in the absence of putative aKIR counterpart are instrumental in antitumor response. These data provide a new framework for improving the utility of genetic risk scores for individualized surveillance.

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.

N-acetylcysteine does not affect the lymphocyte proliferation and natural killer cell activity responses to exercise

1998 ◽  
Vol 275 (4) ◽  
pp. R1227-R1231
Author(s):  
H. B. Nielsen ◽  
N. H. Secher ◽  
M. Kappel ◽  
B. K. Pedersen
Keyword(s):  
Natural Killer ◽  
Lymphocyte Proliferation ◽  
Nk Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Nk Cell Activity ◽  
Double Blind ◽  
Significant Difference ◽  
Ergometer Rowing

This study evaluated whether N-acetylcysteine (NAC) attenuates the reduced lymphocyte proliferation and natural killer (NK) cell activity responses to exercise in humans. Fourteen oarsmen were double-blind randomized to either NAC (6 g daily for 3 days) or placebo groups. During 6-min “all-out” ergometer rowing, the concentration of lymphocytes in the peripheral blood increased, with no significant difference between NAC and placebo as reflected in lymphocyte subsets: CD4+, CD8+, CD16+, and CD19+ cells. The phytohemagglutinin-stimulated lymphocyte proliferation decreased from 9,112 ± 2,865 to 5,851 ± 1,588 cpm ( P < 0.05), but it was not affected by NAC. During exercise, the NK cell activity was elevated from 17 ± 3 to 38 ± 4% and it decreased to 7 ± 1% below the resting value 2 h into recovery. Yet, when evaluated as lytic units per CD16+ cell, the NK cell activity decreased during and after exercise without a significant effect of NAC. We conclude that NAC does not attenuate the reduction in lymphocyte proliferation and NK cell activity associated with intense exercise.

Expression patterns of NKG2A, KIR, and CD57 define a process of CD56dim NK-cell differentiation uncoupled from NK-cell education

Blood ◽  
2010 ◽  
Vol 116 (19) ◽  
pp. 3853-3864 ◽  
Author(s):  
Niklas K. Björkström ◽  
Peggy Riese ◽  
Frank Heuts ◽  
Sandra Andersson ◽  
Cyril Fauriat ◽  
...  
Keyword(s):  
Immune System ◽  
Cell Differentiation ◽  
Nk Cells ◽  
Nk Cell ◽  
Expression Patterns ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Phenotypic Properties ◽  
Hematopoietic Stem ◽  
Nk Cell Differentiation

Abstract Natural killer (NK) cells are lymphocytes of the innate immune system that, following differentiation from CD56bright to CD56dim cells, have been thought to retain fixed functional and phenotypic properties throughout their lifespan. In contrast to this notion, we here show that CD56dim NK cells continue to differentiate. During this process, they lose expression of NKG2A, sequentially acquire inhibitory killer cell inhibitory immunoglobulin-like receptors and CD57, change their expression patterns of homing molecules, and display a gradual decline in proliferative capacity. All cellular intermediates of this process are represented in varying proportions at steady state and appear, over time, during the reconstitution of the immune system, as demonstrated in humanized mice and in patients undergoing hematopoietic stem cell transplantation. CD56dim NK-cell differentiation, and the associated functional imprint, occurs independently of NK-cell education by interactions with self–human leukocyte antigen class I ligands and is an essential part of the formation of human NK-cell repertoires.

scholarly journals IL-17 constrains natural killer cell activity by restraining IL-15–driven cell maturation via SOCS3

2019 ◽  
Vol 116 (35) ◽  
pp. 17409-17418 ◽  
Author(s):  
Xuefu Wang ◽  
Rui Sun ◽  
Xiaolei Hao ◽  
Zhe-Xiong Lian ◽  
Haiming Wei ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Cell Maturation ◽  
Dependent Manner ◽  
Deficient Mice

Increasing evidence demonstrates that IL-17A promotes tumorigenesis, metastasis, and viral infection. Natural killer (NK) cells are critical for defending against tumors and infections. However, the roles and mechanisms of IL-17A in regulating NK cell activity remain elusive. Herein, our study demonstrated that IL-17A constrained NK cell antitumor and antiviral activity by restraining NK cell maturation. It was observed that the development and metastasis of tumors were suppressed in IL-17A–deficient mice in the NK cell-dependent manner. In addition, the antiviral activity of NK cells was also improved in IL-17A–deficient mice. Mechanistically, ablation of IL-17A signaling promoted generation of terminally mature CD27−CD11b+ NK cells, whereas constitutive IL-17A signaling reduced terminally mature NK cells. Parabiosis or mixed bone marrow chimeras from Il17a−/−and wild-type (WT) mice could inhibit excessive generation of terminally mature NK cells induced by IL-17A deficiency. Furthermore, IL-17A desensitized NK cell responses to IL-15 and suppressed IL-15–induced phosphorylation of signal transducer and activator of transcription 5 (STAT5) via up-regulation of SOCS3, leading to down-regulation of Blimp-1. Therefore, IL-17A acts as the checkpoint during NK cell terminal maturation, which highlights potential interventions to defend against tumors and viral infections.

scholarly journals A Unique Enzymatically Hydrolyzed Whey Protein Positively Impacts Measures of Immunity

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1533-1533
Author(s):  
Tory Parker ◽  
Anna Andersen ◽  
David Vollmer
Keyword(s):  
Immune System ◽  
Nutritive Value ◽  
Nk Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Milk Proteins ◽  
Transfer Factors ◽  
Funding Sources ◽  
Immunological Research

Abstract Objectives Milk proteins appear to have little direct impact on the immune system when consumed directly. The digestive system breaks them down into absorbable size and they provide nutritive value. However, it has been discovered that enzymatically hydrolyzed peptides can more directly influence the immune system, presumably before digestion completes their hydrolysis during gut immune system exposure. The term ‘bioactive centers’ will be used to describe these unique peptides. Methods After screening several different versions of enzyme hydrolyzed whey, a new bioactive center-containing product was found that had promise for further immunological research. It was compared against transfer factors, 4Life Research's colostrum filtrate, which have previously been studied for their immune activity. Results In a natural killer cell activity assay, the bioactive centers product was significantly (70%) more effective than IL-2, the standard stimulant, and equally as effective as transfer factors. A second experiment confirmed that this effect was consistent across different production batches of the product. A third experiment found that a combination of the bioactive centers and transfer factors enhanced the activity by 10% on average. In a second study, the bioactive centers were evaluated in a mouse model. They were as effective as transfer factors in stimulating NK cell activity, antibody production, TNF-alpha and IL-2 production, and in stimulating phagocytosis. In most cases, results were higher, though not statistically significantly so, for the transfer factor/bioactive centers combination. Conclusions Since the discovery of transfer factors, work both in and outside of 4Life Research has continued to try to identify new approaches to positively impacting the immune system. These results show that bioactive centers from whey can have such activity. Further work is needed to fully understand their impact in human health. Funding Sources 4Life Research.

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