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Автор: Grafiati

Опубліковано: 18 травня 2024

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1

Maslikova, U. V., E. G. Khamaganova, M. Yu Drokov, I. Yu Urybin, E. D. Mikhaltsova, L. A. Kuzmina, and E. N. Parovichnikova. "Probability of allogeneic hematopoietic stem cell transplant failure depending on the recipient's killer immunoglobulin-like receptor genotype." Transplantologiya. The Russian Journal of Transplantation 15, no. 1 (March 17, 2023): 23–33. http://dx.doi.org/10.23873/2074-0506-2023-15-1-23-33.

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Introduction. Natural killers are the "first line" of antitumor and antiviral protection in the early stages after аllogeneic hematopoietic stem cell transplantation. Quantitative characteristics reach normal values already in the first month after the infusion of blood stem cells to the recipient. Self-tolerance of natural killers is achieved due to many receptors on their surface, but killer immunoglobulin-like receptors play a key role. Their role is to recognize "self" cells and block signals aimed at destroying their own cells. Knowledge of the functional activity of natural killers urged to studying the impact of mismatches between the inhibitory receptor gene and the ligand on the development of allogeneic hematopoietic stem cell transplant failure.The aim of research was to study the probability of the graft failure development in allogeneic hematopoietic stem cell transplantation depending on the recipient's killer immunoglobulin-like receptor genotype.Material and methods. Genotyping of killer-cell immunoglobulin-like receptors in 66 recipients of blood stem cells by the polymerase chain reaction method was performed in the study. Using an online calculator, receptors were classified as "best", "better" and "neutral" depending on the genotype. The end point of the assessment was the development of graft failure in the presence of different genotypes of immunoglobulin-like receptors in the recipient.Results. According to the data obtained, the presence of the “best” and "better" killer-cell immunoglobulin-like receptor genotype in the recipient significantly increased the risks of developing various forms of graft failure.Conclusion. The presence of the KIR2DL3 genotype in a recipient of hematopoietic stem cells significantly (by 3 times) reduces the likelihood of primary graft failure. This result is of great prognostic significance, although at present no ways of influencing it have been developed. The presence of the “best” killer immunoglobulin-like receptors genotype in the recipient increases the likelihood of developing graft failure by more than 3 times compared to the best and neutral genotype (44.4% vs. 13.4%).

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2

Parham, P. "Immunogenetics of killer-cell immunoglobulin-like receptors." Tissue Antigens 62, no. 3 (September 2003): 194–200. http://dx.doi.org/10.1034/j.1399-0039.2003.00126.x.

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3

Parham, Peter. "Immunogenetics of killer cell immunoglobulin-like receptors." Molecular Immunology 42, no. 4 (February 2005): 459–62. http://dx.doi.org/10.1016/j.molimm.2004.07.027.

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4

Fauriat, Cyril, Martin A. Ivarsson, Hans-Gustaf Ljunggren, Karl-Johan Malmberg, and Jakob Michaëlsson. "Education of human natural killer cells by activating killer cell immunoglobulin-like receptors." Blood 115, no. 6 (February 11, 2010): 1166–74. http://dx.doi.org/10.1182/blood-2009-09-245746.

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Abstract Expression of inhibitory killer cell immunoglobulin-like receptors (KIRs) specific for self–major histocompatibility complex (MHC) class I molecules provides an educational signal that generates functional natural killer (NK) cells. However, the effects of activating KIRs specific for self-MHC class I on NK-cell education remain elusive. Here, we provide evidence that the activating receptor KIR2DS1 tunes down the responsiveness of freshly isolated human NK cells to target cell stimulation in donors homozygous for human leukocyte antigen (HLA)–C2, the ligand of KIR2DS1. The tuning was apparent in KIR2DS1+ NK cells lacking expression of inhibitory KIRs and CD94/NKG2A, as well as in KIR2DS1+ NK cells coexpressing the inhibitory MHC class I–specific receptors CD94/NKG2A and KIR2DL3, but not KIR2DL1. However, the tuning of responsiveness was restricted to target cell recognition because KIR2DS1+ NK cells responded well to stimulation with exogenous cytokines. Our results provide the first example of human NK-cell education by an activating KIR and suggest that the education of NK cells via activating KIRs is a mechanism to secure tolerance that complements education via inhibitory KIRs.

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5

Bimber, Benjamin N., and David T. Evans. "The killer-cell immunoglobulin-like receptors of macaques." Immunological Reviews 267, no. 1 (August 18, 2015): 246–58. http://dx.doi.org/10.1111/imr.12329.

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6

Rajalingam, Raja. "Diversity of Killer Cell Immunoglobulin-Like Receptors and Disease." Clinics in Laboratory Medicine 38, no. 4 (December 2018): 637–53. http://dx.doi.org/10.1016/j.cll.2018.08.001.

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7

Momot, T., S. Koch, N. Hunzelmann, T. Krieg, K. Ulbricht, R. E. Schmidt, and T. Witte. "Association of killer cell immunoglobulin-like receptors with scleroderma." Arthritis & Rheumatism 50, no. 5 (2004): 1561–65. http://dx.doi.org/10.1002/art.20216.

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8

Long, Eric O., Domingo F. Barber, Deborah N. Burshtyn, Mathias Faure, Mary Peterson, Sumati Rajagopalan, Valery Renard, et al. "Inhibition of natural killer cell activation signals by killer cell immunoglobulin-like receptors (CD158)." Immunological Reviews 181, no. 1 (July 2001): 223–33. http://dx.doi.org/10.1034/j.1600-065x.2001.1810119.x.

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9

Moretta, Lorenzo, Franco Locatelli, Daniela Pende, Emanuela Marcenaro, Maria Cristina Mingari, and Alessandro Moretta. "Killer Ig–like receptor-mediated control of natural killer cell alloreactivity in haploidentical hematopoietic stem cell transplantation." Blood 117, no. 3 (January 20, 2011): 764–71. http://dx.doi.org/10.1182/blood-2010-08-264085.

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Анотація:

Abstract Natural killer (NK) cells are key members of the innate immune system. In a self-environment, they sense and kill target cells lacking major histocompatibility complex class I molecules and release various cytokines on activation. The discovery of human leukocyte antigen (HLA) class I specific inhibitory receptors (including the allotype-specific killer immunoglobulin-like receptors), and of various activating receptors and their ligands, provided the basis for understanding the molecular mechanism of NK-cell activation and function, mainly resulting from the balance between activating and inhibitory signals. In an allogeneic setting, such as T cell–depleted haploidentical hematopoietic stem cell transplantation, NK cells may express inhibitory killer immunoglobulin-like receptors that are not engaged by any of the HLA class I alleles present on allogeneic cells. Such “alloreactive” NK cells greatly contribute both to eradication of leukemia blasts escaping the preparative regimen and to clearance of residual host dendritic cells and T lymphocytes (thus preventing graft-versus-host disease and graft rejection, respectively). Improved prevention of graft-versus-host disease might be achieved by redirecting to lymph nodes adoptively transferred, alloreactive NK cells by inducing CCR7-uptake in vitro. Recent studies suggested that, after immune-suppressive therapy, alloreactive NK cells from an HLA-haploidentical donor may prevent leukemia recurrence also in patients who have not received allogeneic hematopoietic stem cell transplantation.

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10

Rajalingam, Raja. "Human diversity of killer cell immunoglobulin-like receptors and disease." Korean Journal of Hematology 46, no. 4 (2011): 216. http://dx.doi.org/10.5045/kjh.2011.46.4.216.

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11

Sala Elpidio, Laise Nayana, Josiane Bazzo de Alencar, Patrícia Yumeko Tsuneto, Hugo Vicentin Alves, Mariana Trento Toretta, Sérgio Ken It Taura, Jeane Eliete Laguila Visentainer, and Ana Maria Sell. "Killer-cell immunoglobulin-like receptors associated with polycystic ovary syndrome." Journal of Reproductive Immunology 130 (November 2018): 1–6. http://dx.doi.org/10.1016/j.jri.2018.08.003.

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12

Velardi, Andrea, Loredana Ruggeri, and Antonella Mancusi. "Killer-cell immunoglobulin-like receptors reactivity and outcome of stem cell transplant." Current Opinion in Hematology 19, no. 4 (July 2012): 319–23. http://dx.doi.org/10.1097/moh.0b013e32835423c3.

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13

Grzywacz, Bartosz, Nandini Kataria, Niketa Kataria, Bruce R. Blazar, Jeffrey S. Miller, and Michael R. Verneris. "Natural killer–cell differentiation by myeloid progenitors." Blood 117, no. 13 (March 31, 2011): 3548–58. http://dx.doi.org/10.1182/blood-2010-04-281394.

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Abstract Because lymphoid progenitors can give rise to natural killer (NK) cells, NK ontogeny has been considered to be exclusively lymphoid. Here, we show that rare human CD34+ hematopoietic progenitors develop into NK cells in vitro in the presence of cytokines (interleukin-7, interleukin-15, stem cell factor, and fms-like tyrosine kinase-3 ligand). Adding hydrocortisone and stromal cells greatly increases the frequency of progenitor cells that give rise to NK cells through the recruitment of myeloid precursors, including common myeloid progenitors and granulocytic-monocytic precursors to the NK-cell lineage. WNT signaling was involved in this effect. Cells at more advanced stages of myeloid differentiation (with increasing expression of CD13 and macrophage colony-stimulating factor receptor [M-CSFR]) could also differentiate into NK cells in the presence of cytokines, stroma, and hydrocortisone. NK cells derived from myeloid precursors (CD56−CD117+M-CSFR+) showed more expression of killer immunoglobulin-like receptors, a fraction of killer immunoglobulin–like receptor-positive–expressing cells that lacked NKG2A, a higher cytotoxicity compared with CD56−CD117+M-CSFR− precursor-derived NK cells and thus resemble the CD56dim subset of NK cells. Collectively, these studies show that NK cells can be derived from the myeloid lineage.

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14

Miyazaki, Kana, Motoko Yamaguchi, Hiroshi Imai, Tohru Kobayashi, Satoshi Tamaru, Kazuhiro Nishii, Masao Yuda, Hiroshi Shiku та Naoyuki Katayama. "Gene expression profiling of peripheral T-cell lymphoma including γδ T-cell lymphoma". Blood 113, № 5 (29 січня 2009): 1071–74. http://dx.doi.org/10.1182/blood-2008-07-166363.

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Abstract The gene expression profile of peripheral γδ T-cell lymphoma (γδTCL) has not been investigated. Using oligonucleotide microarrays, we analyzed total RNA from 7 patients with γδTCL (4 hepatosplenic, 1 cutaneous, 1 intestinal, and 1 thyroidal) and 27 patients with αβTCL (11 peripheral TCL-unspecified, 15 angioimmunoblastic TCL, and 1 hepatosplenic). Unsupervised microarray analyses classified all hepatosplenic γδTCLs into a single cluster, whereas other γδTCLs were scattered within the αβTCL distribution. We identified a T-cell receptor signature gene set, which accurately classified γδTCL and αβTCL. A classifier based on gene expression under supervised analysis correctly identified γδTCL. One case of hepatosplenic αβTCL was placed in the γδTCL grouping. γδTCL signature genes included genes encoding killer cell immunoglobulin-like receptors and killer cell lectin-like receptors. Our results indicate that hepatosplenic γδTCL is a distinct form of peripheral TCL and suggest that nonhepatosplenic γδTCLs are heterogeneous in gene expression.

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15

Contreras, G., C. Aláez, A. Murguía, D. García, H. Flores, and C. Gorodezky. "Distribution of the killer cell immunoglobulin-like receptors in Mexican Mestizos." Tissue Antigens 69 (April 2007): 125–29. http://dx.doi.org/10.1111/j.1399-0039.2006.76212.x.

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16

Alvarado-Hernández, D. L., A. Benítez-Sánchez, J. S. Rodríguez-Cuevas, T. Rosales-Saavedra, S. E. Guerra-Palomares, A. Comas-García, D. E. Noyola, and C. A. García-Sepúlveda. "Killer-cell immunoglobulin-like receptors and cytomegalovirus reactivation during late pregnancy." International Journal of Immunogenetics 43, no. 4 (June 9, 2016): 189–99. http://dx.doi.org/10.1111/iji.12271.

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17

Blunt, Matthew D., and Salim I. Khakoo. "Activating killer cell immunoglobulin‐like receptors: Detection, function and therapeutic use." International Journal of Immunogenetics 47, no. 1 (November 22, 2019): 1–12. http://dx.doi.org/10.1111/iji.12461.

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18

Lowe, D. P., M. A. Cook, S. J. Bowman, and D. C. Briggs. "Association of killer cell immunoglobulin-like receptors with primary Sjogren's syndrome." Rheumatology 48, no. 4 (January 30, 2009): 359–62. http://dx.doi.org/10.1093/rheumatology/ken503.

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19

Colucci, Francesco, and James Traherne. "Killer-cell immunoglobulin-like receptors on the cusp of modern immunogenetics." Immunology 152, no. 4 (September 12, 2017): 556–61. http://dx.doi.org/10.1111/imm.12802.

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20

Olaniyan, Subulade A., Olukemi K. Amodu, Louis-Marie Yindom, David J. Conway, Peter Aka, Adekunle A. Bakare, and Olayemi O. Omotade. "Killer-cell immunoglobulin-like receptors and falciparum malaria in southwest Nigeria." Human Immunology 75, no. 8 (August 2014): 816–21. http://dx.doi.org/10.1016/j.humimm.2014.06.002.

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21

Niokou, Dimitra, Maria Spyropoulou-Vlachou, Areti Darlamitsou, and Catherine Stavropoulos-Giokas. "Distribution of killer cell immunoglobulin-like receptors in the Greek population." Human Immunology 64, no. 12 (December 2003): 1167–76. http://dx.doi.org/10.1016/j.humimm.2003.08.100.

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22

Hidajat, Melanny, Dominik Selleslag, Achiel Van Hoof, Jan Van Droogenbroeck, Johan Billiet, and Arnold Criel. "Killer Immunoglobulin-Like Receptors (KIRs) Genotypes in a Belgian Population." Blood 104, no. 11 (November 16, 2004): 3852. http://dx.doi.org/10.1182/blood.v104.11.3852.3852.

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Abstract KIRs (Killer cell Immunoglobulin-like Receptors) are expressed on NK (Natural Killer) cells and a subpopulation of T lymphocytes namely memory CD8+ T cells. The distribution of KIR genes varies among individuals and populations. These genes are encoded on chromosome 19 (19q13.4). Till now 17 KIR genes and pseudogenes have been identified. KIRs recognise groups of HLA class I alleles. NK activity is partially controlled through the interaction between KIRs and their HLA ligands. Several studies report that KIRs may affect the outcome of Hematopoietic Stem-Cell Transplantations. We performed KIR typing of 17 genes and pseudogenes in 100 healthy Belgian unrelated individuals in “West-Vlaanderen” from Caucasoid origin using a PCR-SSP method. Three genes (KIR3DL3, 2DL4 and 3DL2), named frame-work genes, and the pseudogene 3DP1 were found in all individuals. KIR2DL1 and 2DP1 genes were present in a frequency of 99%. In addition, KIR3DL1 and 2DS4 genes represented a frequency of 97. The KIR2DL3 was found in 90% and the frequencies of other genes varied between 56% and 24%. The individual KIR gene content ranged from 8 to 17 genes. A total of 19 KIR locus profiles was observed. The most common KIR locus profile (32%) consisted of a combination of genes characterising A haplotypes (KIR2DL1 and 2DL3) without the presence of genes characteristic of B haplotypes (KIR2DL2 and 2DS2). The second most common KIR locus profile, accounting for 20% contained a combination of genes characteristics for both A and B haplotypes. The allele KIR2DS4*003 was found in 89% and KIR2DS4*00101/00102/002 only in 41%. KIR3DP1*00301/00302 was present in all individuals and KIR3DP1*001/002 only in 35%. Our results show that frequencies of most KIR loci in our Belgian population were comparable to literature data of other Caucasian populations. Only KIR2DS1 was lower (27% vs 47.7% with a p-value of 0.0002). In the future, KIR typing of donor and patient before a Hematopoietic Stem-cell Transplantation may be necessary, due to the diversity in KIR genotypes.

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23

McVicar, D. W., and D. N. Burshtyn. "Intracellular Signaling by the Killer Immunoglobulin-Like Receptors and Ly49." Science Signaling 2001, no. 75 (March 27, 2001): re1. http://dx.doi.org/10.1126/stke.2001.75.re1.

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24

Gardiner, Clair M. "Killer cell immunoglobulin-like receptors on NK cells: the how, where and why." International Journal of Immunogenetics 35, no. 1 (December 18, 2007): 1–8. http://dx.doi.org/10.1111/j.1744-313x.2007.00739.x.

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25

Chrul, Slawomir, Ewa Polakowska, Agnieszka Szadkowska, and Jerzy Bodalski. "Influence of Interleukin IL-2 and IL-12 + IL-18 on Surface Expression of Immunoglobulin-Like Receptors KIR2DL1, KIR2DL2, and KIR3DL2 in Natural Killer Cells." Mediators of Inflammation 2006 (2006): 1–6. http://dx.doi.org/10.1155/mi/2006/46957.

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Natural killer (NK) cells express killer cell inhibitory receptors (KIRs) that recognize polymorphic class I MHC molecules. In the present study, we analyze the modulatory effect of IL-2 alone or a combination of IL-12 with IL-18 on surface expression of killer cell immunoglobulin-like receptors KIR2DL1, KIR2DL2, and KIR3DL2 in NK cells. Thus, it was found that IL-2 causes a significant increase in the proportion of cells with given studied receptors. Stimulation by a mixture of IL-12 and IL-18 caused significant increase in the fraction of cells with the KIR2DL1 and KIR2DL2, however no significant change in the percentage of cells with KIR3DL2 receptor on their surface was observed. The results of the study show the presence of KIRs on both resting and activated NK cells, this may suggest that KIRs have also an important role in the regulatory processes after activation of this subpopulation of cells.

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26

Mulrooney, Tiernan J., Phillip E. Posch, and Carolyn Katovich Hurley. "DAP12 impacts trafficking and surface stability of killer immunoglobulin-like receptors on natural killer cells." Journal of Leukocyte Biology 94, no. 2 (May 28, 2013): 301–13. http://dx.doi.org/10.1189/jlb.0213093.

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27

Henel, Gabriella, Karnail Singh, Dapeng Cui, Sergey Pryshchep, Won-Woo Lee, Cornelia M. Weyand, and Jörg J. Goronzy. "Uncoupling of T-cell effector functions by inhibitory killer immunoglobulin–like receptors." Blood 107, no. 11 (June 1, 2006): 4449–57. http://dx.doi.org/10.1182/blood-2005-06-2519.

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AbstractKiller immunoglobulin–like receptors (KIRs) are a family of regulatory cell-surface molecules expressed on natural killer (NK) cells and memory T-cell subsets. Their ability to prevent the formation of an activation platform and to inhibit NK cell activation is the basis of the missing self model of NK cell function. The benefits of KIR expression for T-cell biology are unclear. We studied how KIR2DL2 regulates T-cell function. Engagement of KIR2DL2 by the ligand human leukocyte antigen (HLA)–Cw3 did not affect conjugate formation between CD4+KIR2DL2+ T cells and superantigen-pulsed target cells or the development of mature immune synapses with lipid rafts. KIR2DL2 and the corresponding HLA-C ligand were initially recruited to the peripheral supramolecular activation cluster (pSMAC). Consequently, KIR2DL2 engagement did not inhibit the phosphorylation of early signaling proteins and T-cell–receptor (TCR)–mediated cytotoxicity or granule exocytosis. After 15-30 minutes, KIR2DL2 moved to the central supramolecular activation cluster (cSMAC), colocalizing with CD3. TCR synapses dissociated, and phosphorylated phospholipase C (PLC)–γ1, Vav1, and extracellular signal–regulated kinase 1/2 (ERK1/2) were reduced 90 minutes after stimulation. Gene array studies documented that the inhibition of late signaling events by KIR2DL2 affected transcriptional gene activation. We propose that KIRs on memory T cells operate to uncouple effector functions by modifying the transcriptional profile while leaving granule exocytosis unabated.

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28

Vojvodic, Svetlana, and Stevan Popovic. "Natural killer cells: Biology, functions and clinical relevance." Medical review 63, no. 1-2 (2010): 91–97. http://dx.doi.org/10.2298/mpns1002091v.

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Анотація:

Introduction. Natural Killer cells (NK cells) represent the subset of peripheral lymphocytes that play critical role in the innate immune response to virus-infected and tumor transformed cells. Lysis of NK sensitive target cells could be mediated independently of antigen stimulation and without requirement of peptide presentation by the major histocompatibility complex (MHC) molecules. NK cell activity and functions are controlled by a considerable number of cell surface receptors, which exist in both inhibitory and activating isoforms. There are several groups of NK cell surface receptors: 1) killer immunoglobulin like receptors-KIR, 2) C-type lectin receptors,3)natural citotoxicity receptors-NCR and 4) Toll-like receptors-TLR. Functions of NK receptors. Defining the biology of NK cell surface receptors has contributed to the concept of the manner how NK cells selectively recognize and lyse tumor and virally infected cells while sparing normal cells. Further, identification of NK receptor ligands and their expression on the normal and transformed cells has led to the development of clinical approaches to manipulating receptor/ligand interactions that showed clinical benefit. NK cells are the first lymphocyte subset that reconstitute the peripheral blood following allogeneic HSCT and multiple roles for alloreactive donor NK cells have been demonstrated, in diminishing Graft vs. Host Disease (GvHD) through selective killing recipient dendritic cells, prevention of graft rejection by killing recipient T cells and participation in Graft vs. Leukaemia (GvL) effect through destruction of residual host tumor cells. Conclusion. Besides their role in HSCT, NK cell receptors have an important clinical relevance that reflects from the fact that they play a crucial role in the development of some diseases as well as in possibilities of managing all NK receptors through selective expansion and usage of NK cells in cancer immunotherapy.

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29

Rajagopalan, Sumati, and Eric O. Long. "Understanding how combinations of HLA and KIR genes influence disease." Journal of Experimental Medicine 201, no. 7 (April 4, 2005): 1025–29. http://dx.doi.org/10.1084/jem.20050499.

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Анотація:

Combinations of HLA and killer cell immunoglobulin–like receptor (KIR) genes have been associated with diseases as diverse as autoimmunity, viral infections, reproductive failure, and now cancer. Much as early observations of disease associations with HLA polymorphism preceded a detailed knowledge of HLA recognition by T cell receptors, the recently reported disease associations with HLA–KIR gene combinations beg for a better understanding of the underlying mechanisms.

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30

Luc-Aimé, Kagoué Simeni, Yindom Louis-Marie, Loni Ekali Gabriel, Clauvis Kunkeng Yengo, F. Esemu Livo, and Nguedia Jules Clement Assob. "Killer-Cell Immunoglobulin-Like Receptors (KIR) in HIV-Exposed Infants in Cameroon." Journal of Immunology Research 2021 (January 13, 2021): 1–7. http://dx.doi.org/10.1155/2021/9053280.

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Анотація:

The biological reason(s) behind persistent mother-to-child transmission (MTCT) of HIV (albeit at reduced rate compared to the preantiretroviral therapy era) in spite of the successful implementation of advanced control measures in many African countries remains a priority concern to many HIV/AIDS control programs. This may be partly due to differences in host immunogenetic factors in highly polymorphic regions of the human genome such as those encoding the killer-cell immunoglobulin-like receptor (KIR) molecules which modulate the activities of natural killer cells. The primary aim of this study was to determine the variants of KIR genes that may have a role to play in MTCT in a cohort of infants born to HIV-infected mothers in Yaoundé, Cameroon. We designed a cross-sectional study to molecularly determine the frequencies of 15 KIR genes in 14 HIV-exposed infected (HEI), 39 HIV-exposed/uninfected (HEU), and 27 HIV-unexposed/uninfected (HUU) infants using the sequence specific primer polymerase chain reaction (PCR-SSP) method. We found that all 15 KIR genes were present in our cohort. The frequency of KIR2DL1 was significantly higher in the unexposed (control) group than in the HIV-exposed group ( OR = 0.22 , P = 0.006 ). Stratifying analysis by infection status but focusing only on exposed infants revealed that KIR2DL5, KIR2DS1, and KIR2DS5 were significantly overrepresented among the HIV-exposed/uninfected compared to infected infants ( OR = 0.20 , P = 0.006 ). Similarly, the frequencies of KIR2DS1, KIR2DS5, and KIR2DL5 were significantly different between infants perinatally infected with HIV (HIV+ by 6 months of age) and HIV-negative infants. Our study demonstrates that KIR genes may have differential effects with regard to MTCT of HIV-1.

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31

Mahfouz, R., R. Rayes, Z. Mahfoud, A. Bazarbachi, and G. Zaatari. "Distribution of killer cell immunoglobulin-like receptors genotypes in the Lebanese population." Tissue Antigens 68, no. 1 (July 2006): 66–71. http://dx.doi.org/10.1111/j.1399-0039.2006.00605.x.

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32

Martinez-Borra, J., and S. I. Khakoo. "Speed and selection in the evolution of killer-cell immunoglobulin-like receptors." International Journal of Immunogenetics 35, no. 2 (April 2008): 89–96. http://dx.doi.org/10.1111/j.1744-313x.2008.00756.x.

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33

Franceschi, Danilo Santana Alessio, Cármino Antonio de Souza, Francisco José Penteado Aranha, Daniela Maira Cardozo, Ana Maria Sell, and Jeane Eliete Laguila Visentainer. "Importance of killer immunoglobulin-like receptors in allogeneic hematopoietic stem cell transplantation." Revista Brasileira de Hematologia e Hemoterapia 33, no. 2 (2011): 126–30. http://dx.doi.org/10.5581/1516-8484.20110033.

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34

Díaz-Peña, R., M. J. de los Santos, Alejandro Lucia, and P. Castro-Santos. "Understanding the role of killer cell immunoglobulin-like receptors in pregnancy complications." Journal of Assisted Reproduction and Genetics 36, no. 5 (March 7, 2019): 827–35. http://dx.doi.org/10.1007/s10815-019-01426-9.

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35

Hassan, Norfarazieda, Le Jie Lee, Jun Hao Tan, Siti Zuleha Idris, Hishamshah Mohd Ibrahim, Raudhawati Osman, Heng Fong Seow, Norhafizah Mohtaruddin, Andi Anggeriana Andi Asri, and Maha Abdullah. "Expression of Killer Cell Immunoglobulin-like Receptors (KIR) in Sex-associated Malignancies." JULY ISSUE 18, no. 4 (July 1, 2022): 96–103. http://dx.doi.org/10.47836//mjmhs18.4.14.

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Introduction: Sex shapes immune response with possible consequence on tumor immune escape. Acute lymphoblastic leukemia (ALL) predominates in males while ovarian cancer (OC) occurs in females. NK cells essential for tumor killing may have male preponderance. Association of sex, NK cell activity and malignancies is unclear. We hypothesize that sex differentially affects KIR expressions in sex-biased cancers. Method: Expression of inhibitory (KIR2DL1-5 and KIR3DL1-3) and activating (KIR2DS1-2 and 4-5 and KIR3DS1) genes in B-, T-cell ALL, OC and normal controls were determined by reverse-transcription polymerase-chain-reaction. Result: All normal males (but not females) expressed the framework genes and generally maintained haplotype A, except KIR3DL1. Normal females expressed more activating KIRs. Frequencies of KIR2DL1, 2DL4 and 2DS2 were significantly reduced among ovarian cancer patients. Sex difference in frequencies of KIR expression was not detected in ALL as majority were undetectable except framework gene KIR3DL2, was more frequent among T-ALL. Conclusion: Cancers may be associated with reduced KIR expression and influence of sex requires investigation.

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36

Wright, Laura, Fionnuala Williams, Derek Middleton, and Deborah Sage. "The role of killer cell immunoglobulin-like receptors in recurrent spontaneous abortion." Human Immunology 65, no. 9-10 (September 2004): S70. http://dx.doi.org/10.1016/j.humimm.2004.07.131.

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37

Hou, LiHua, Noriko K. Steiner, Minghua Chen, Ian Belle, Anna L. Kubit, Jennifer Ng, and Carolyn Katovich Hurley. "Limited allelic diversity of stimulatory two-domain killer cell immunoglobulin-like receptors." Human Immunology 69, no. 3 (March 2008): 174–78. http://dx.doi.org/10.1016/j.humimm.2008.01.009.

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38

Gumá, Mónica, Ana Angulo, Carlos Vilches, Natalia Gómez-Lozano, Núria Malats, and Miguel López-Botet. "Imprint of human cytomegalovirus infection on the NK cell receptor repertoire." Blood 104, no. 12 (December 1, 2004): 3664–71. http://dx.doi.org/10.1182/blood-2004-05-2058.

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Expression of the activating CD94/NKG2C killer lectin-like receptor (KLR) specific for HLA-E was analyzed in peripheral blood lymphocytes (PBLs) from healthy adult blood donors; the expression of other natural killer (NK) cell receptors (ie, CD94/NKG2A, KIR, CD85j, CD161, NKp46, NKp30, and NKG2D) was also studied. Human cytomegalovirus (HCMV) infection as well as the HLA-E and killer immunoglobulin-like receptor (KIR) genotypes were considered as potentially relevant variables associated with CD94/NKG2C expression. The proportion of NKG2C+ lymphocytes varied within a wide range (<0.1% to 22.1%), and a significant correlation (r = 0.83; P < .001) between NKG2C+ NK and T cells was noticed. The HLA-E genotype and the number of activating KIR genes of the donors were not significantly related to the percentage of NKG2C+ lymphocytes. By contrast, a positive serology for HCMV, but not for other herpesviruses (ie, Epstein-Barr and herpes simplex), turned out to be strongly associated (P < .001) with increased proportions of NKG2C+ NK and T cells. Remarkably, the CD94/NKG2C+ population expressed lower levels of natural cytotoxicity receptors (NCRs) (ie, NKp30, NKp46) and included higher proportions of KIR+ and CD85j+ cells than CD94/NKG2A+ cells. Altogether, these data support that HCMV infection selectively shapes the natural killer cell receptor (NKR) repertoire of NK and T cells from healthy carrier individuals.

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39

Cremer, Anja, Ute Heider, Stefan Tomiuk, Andreas Arendt, Jurgen Schmitz, Andreas Bosio, Volker Huppert, and Christian Biervert. "Integrated Genotyping and mRNA Expression Profiling of Killer Immunoglobulin-Like Receptors." Blood 106, no. 11 (November 16, 2005): 3909. http://dx.doi.org/10.1182/blood.v106.11.3909.3909.

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Abstract Natural killer (NK) cells belong to a subgroup of lymphocytes (CD3-CD56+) which play an important role in the cellular immune response against virus-infected cells and tumors. The activity of NK cells is regulated by a balance of triggering and inhibitory receptors, including Killer Ig-like Receptor (KIR) molecules which interact with specific HLA class I molecules, predominantly HLA-C, on target cells. The 17 known KIR genes are divided into two classes: activating KIRs and inhibitory KIRs. There is strong evidence that inhibitory KIR mismatch between donor and recipient improves the outcome of haploidentical hematopoietic stem cell transplantation (HSTC) in leukemia patients (Ruggeri et al. 2002). In addition, the KIR-HLA constellation is assumed to have an influence on the severity of graft versus host disease (GvHD). Whether these activities of NK cells are clinically important and to what extent these processes are mediated only by KIR-HLA class I interactions remains to be determined. In human populations, KIR gene haplotypes vary in the number and type of KIR genes they contain. Further diversification is observed by expanded allelic polymorphism at the individual genes. In general, KIR haplotypes contain 7–12 genes plus 2 pseudogenes. Extra KIR heterogeneity is provided at the expression level: different subsets of NK cells within an individual express different KIRs. Recently, it was shown that KIR genotyping alone does not seem to be sufficient for donor KIR assessment because of the lack of gene expression in approximately one-fourth of the individuals for one of the inhibitory KIRs that recognize the three major groups of MHC class I ligands (Leung et al. 2005). KIR phenotyping by flow cytometry using monoclonal antibodies is insufficient due to the lack of specific monoclonal antibodies. For trustworthy analysis, one has to combine KIR genotyping with mRNA expression profiling and flow cytometry. Therefore, we developed a new set of sequence-specific primers (SSP). This primer set can be applied to perform either KIR genotyping or mRNA expression profiling despite the high degree of identity of the genes (80–90%, sometimes more than 95%). The primers of each KIR gene (15 genes and 2 pseudogenes) cover all allelic variants annotated by the IPD KIR Sequence Data Base (status quo July 05). Using this primer set, we genotyped 25 individuals, and compared the results with other sets of KIR primers published elsewhere. Additionally, we show the mRNA expression profile employing the same set of new primers. We confirmed these results on the protein level by flow cytometry.

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40

Han, Mei, Margarita Fallena, Yuhong Guo, and Peter Stastny. "Natural killer cell crossmatch: Functional analysis of inhibitory killer immunoglobulin-like receptors and their HLA ligands." Human Immunology 68, no. 6 (June 2007): 507–13. http://dx.doi.org/10.1016/j.humimm.2007.02.001.

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41

Colonna, Marco, Francisco Navarro, Teresa Bellón, Manuel Llano, Pilar García, Jacqueline Samaridis, Lena Angman, Marina Cella, and Miguel López-Botet. "A Common Inhibitory Receptor for Major Histocompatibility Complex Class I Molecules on Human Lymphoid and Myelomonocytic Cells." Journal of Experimental Medicine 186, no. 11 (December 1, 1997): 1809–18. http://dx.doi.org/10.1084/jem.186.11.1809.

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Natural killer (NK) cell–mediated lysis is negatively regulated by killer cell inhibitory receptors specific for major histocompatibility complex (MHC) class I molecules. In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells. This receptor, called Ig-like transcript (ILT)2, binds MHC class I molecules and delivers a negative signal that inhibits killing by NK and T cells, as well as Ca2+ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and human histocompatibility leukocyte antigens (HLA)–DR, respectively. In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules. These results suggest that diverse leukocyte lineages have adopted recognition of self–MHC class I molecules as a common strategy to control cellular activation during an immune response.

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42

Rettman, Pauline, Matthew D. Blunt, Rebecca J. Fulton, Andres F. Vallejo, Leidy Y. Bastidas-Legarda, Laura España-Serrano, Marta E. Polak, Aymen Al-Shamkhani, Christelle Retiere, and Salim I. Khakoo. "Peptide: MHC-based DNA vaccination strategy to activate natural killer cells by targeting killer cell immunoglobulin-like receptors." Journal for ImmunoTherapy of Cancer 9, no. 5 (May 2021): e001912. http://dx.doi.org/10.1136/jitc-2020-001912.

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BackgroundNatural killer (NK) cells are increasingly being recognized as agents for cancer immunotherapy. The killer cell immunoglobulin-like receptors (KIRs) are expressed by NK cells and are immunogenetic determinants of the outcome of cancer. In particular, KIR2DS2 is associated with protective responses to several cancers and also direct recognition of cancer targets in vitro. Due to the high homology between activating and inhibitory KIR genes to date, it has been challenging to target individual KIR for therapeutic benefit.MethodsA novel KIR2DS2-targeting therapeutic peptide:MHC DNA vaccine was designed and used to immunize mice transgenic for KIR genes (KIR-Tg). NK cells were isolated from the livers and spleens of vaccinated mice and then analyzed for activation by flow cytometry, RNA profiling and cytotoxicity assays. In vivo assays of NK cell function using a syngeneic cancer model (B16 melanoma) and an adoptive transfer model for human hepatocellular carcinoma (Huh7) were performed.ResultsInjecting KIR-Tg mice with the vaccine construct activated NK cells in both liver and spleens of mice, with preferential activation of KIR2DS2-positive NK cells. KIR-specific activation was most marked on the CD11b+CD27+ mature subset of NK cells. RNA profiling indicated that the DNA vaccine upregulated genes associated with cellular metabolism and downregulated genes related to histone H3 methylation, which are associated with immune cell maturation and NK cell function. Vaccination led to canonical and cross-reactive peptide:MHC-specific NK cell responses. In vivo, DNA vaccination led to enhanced antitumor responses against B16F10 melanoma cells and also enhanced responses against a tumor model expressing the KIR2DS2 ligand HLA-C*0102.ConclusionWe show the feasibility of a peptide-based KIR-targeting vaccine strategy to activate NK cells and hence generate functional antitumor responses. This approach does not require detailed knowledge of the tumor peptidomes nor HLA matching with the patient. It therefore offers a novel opportunity for targeting NK cells for cancer immunotherapy.

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Vey, Norbert, and Daniel Olive. "Anti-natural Killer Inhibitory Receptors in Elderly Patients with Acute Myeloid Leukaemia." European Oncology & Haematology 06, no. 01 (2010): 86. http://dx.doi.org/10.17925/eoh.2010.06.1.86.

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Treatment with anti-killer-cell immunoglobulin-like receptor (KIR) monoclonal antibody (mAb) is a new approach aimed at harnessing the antileukaemic potential of natural killer (NK) cells for the treatment of acute myeloid leukaemia (AML). NK cell antitumour activity is regulated by a balance between activating and inhibitory receptors (KIR). 1-7F9/IPH2101 is a fully human immunoglobulin G4 (IgG4) mAb that binds to inhibitory KIR and blocks binding with its ligand (human leukocyte antigen C [HLA-C] molecule) on leukaemic cells.In vitro,and in a surrogatein vivomodel in mice, treatment with 1-7F9/IPH2101 was able to induce NK cell activation and cytotoxicity against leukaemic cells. Patients with AML often display abnormal NK cell function, while evidence of an impact of NK cell status on AML outcome has been reported in allogeneic transplantation. 1-7F9/IPH2101 is currently under clinical investigation in patients with AML. This article reviews the mechanisms of NK cell antileukaemic activity and its role and defects in AML. Currently available data on the pre-clinical and clinical development of 1-7F9/IPH2101 are presented, and the rationale for its future use as a single agent or in combination is discussed.

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Allan, David S. J., Marco Colonna, Lewis L. Lanier, Tatyana D. Churakova, John S. Abrams, Shirley A. Ellis, Andrew J. McMichael, and Veronique M. Braud. "Tetrameric Complexes of Human Histocompatibility Leukocyte Antigen (HLA)-G Bind to Peripheral Blood Myelomonocytic Cells." Journal of Experimental Medicine 189, no. 7 (April 5, 1999): 1149–56. http://dx.doi.org/10.1084/jem.189.7.1149.

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The nonclassical MHC class I molecule human histocompatibility leukocyte antigen (HLA)-G is selectively expressed on fetal trophoblast tissue at the maternal–fetal interface in pregnancy. It has long been suggested that HLA-G may inhibit maternal natural killer (NK) cells through interaction with particular NK cell receptors (KIRs). To investigate interactions of HLA-G, we constructed phycoerythrin-labeled tetrameric complexes of HLA-G refolded with a self-peptide. These HLA-G tetramers failed to bind to NK cells and cells transfected with CD94/NKG2 and killer immunoglobulin-like NK receptors. In contrast, HLA-G tetramers did bind to peripheral blood monocytes, staining a CD16+CD14mid subset with greater intensity. On transfectants, HLA-G tetramers bound to inhibitory immunoglobulin-like transcript (ILT)2 and ILT4 receptors. However, staining in the presence of antibodies reactive with ILT receptors revealed that the interaction of HLA-G tetramers with blood monocytes was largely due to binding to ILT4. These results suggest that the primary role of HLA-G may be the modulation of myelomonocytic cell behavior in pregnancy.

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45

Foley, Bree, Sarah Cooley, Michael R. Verneris, Michelle Pitt, Julie Curtsinger, Xianghua Luo, Sandra Lopez-Vergès, Lewis L. Lanier, Daniel Weisdorf, and Jeffrey S. Miller. "Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function." Blood 119, no. 11 (March 15, 2012): 2665–74. http://dx.doi.org/10.1182/blood-2011-10-386995.

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AbstractDuring mouse cytomegalovirus (CMV) infection, a population of Ly49H+ natural killer (NK) cells expands and is responsible for disease clearance through the induction of a “memory NK-cell response.” Whether similar events occur in human CMV infection is unknown. In the present study, we characterized the kinetics of the NK-cell response to CMV reactivation in human recipients after hematopoietic cell transplantation. During acute infection, NKG2C+ NK cells expanded and were potent producers of IFNγ. NKG2C+ NK cells predominately expressed killer cell immunoglobulin–like receptor, and self-killer cell immunoglobulin–like receptors were required for robust IFNγ production. During the first year after transplantation, CMV reactivation induced a more mature phenotype characterized by an increase in CD56dim NK cells. Strikingly, increased frequencies of NKG2C+ NK cells persisted and continued to increase in recipients who reactivated CMV, whereas these cells remained at low frequency in recipients without CMV reactivation. Persisting NKG2C+ NK cells lacked NKG2A, expressed CD158b, preferentially acquired CD57, and were potent producers of IFNγ during the first year after transplantation. Recipients who reactivated CMV also expressed higher amounts of IFNγ, T-bet, and IL-15Rα mRNA transcripts. Our findings support the emerging concept that CMV-induced innate memory-cell populations may contribute to malignant disease relapse protection and infectious disease control long after transplantation.

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46

Mulrooney, Tiernan, and Carolyn Hurley. "DAP12 impacts trafficking and surface stability of killer immunoglobulin-like receptors on natural killer cells (P1323)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 63.16. http://dx.doi.org/10.4049/jimmunol.190.supp.63.16.

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Abstract Killer Ig-like receptors (KIR) aid in the regulation of natural killer (NK) cell activity. In this study, the effect of the interaction between the two domain stimulatory KIR (KIR2DS) and their adapter, DAP12, was investigated beyond the previously defined signaling function. Flow cytometry analysis showed enhanced KIR2DS surface expression on NKL cells when co-transfected with DAP12. Conversely, KIR2DS4 surface expression on primary cells was decreased when the cells were treated with DAP12 specific siRNA. Treatment of the KIR2DS and DAP12 transfected cells with either cycloheximide or Brefeldin A repressed KIR2DS surface expression revealing a role for DAP12 in trafficking newly synthesized KIR to the cell surface. Immunoprecipitation of DAP12 revealed an interaction of DAP12 with an immature isoform of KIR2DS indicating the interaction likely initiates within the endoplasmic reticulum. An internalization assay demonstrated a significant impact of DAP12 on KIR2DS surface stability. Confocal microscopy showed internalized KIR2DS molecules are recruited to lysosomal compartments independent of DAP12 expression. Our results suggest in vivo conditions that adversely affect DAP12 expression will indirectly reduce surface expression and stability of KIR2DS. These effects could significantly impact ligand recognition and strength of signaling through KIR2DS molecules.

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47

Schellekens, Jennifer, Anna Stserbakova, Madis Tõns, Hele Everaus, Marcel GJ Tilanus, and Alar Aints. "HLA Influence on NK Cell Expansion." Blood 112, no. 11 (November 16, 2008): 4924. http://dx.doi.org/10.1182/blood.v112.11.4924.4924.

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Abstract Natural Killer (NK) cells are effector cells in the innate immune system. The anti-leukaemic capacities of NK cells in haematopoietic stem cell transplantation make these cells a potential treatment modality to improve clinical outcome. Immunotherapy with NK cells requires transfusion of large quantities, which obviates the need for an in vitro culture system for NK cells. The killer cell immunoglobulin-like receptors (KIR) on NK cells recognise defined groups of HLA class I alleles. To elucidate the influence of these interactions on proliferation, the peripheral blood mononuclear cells (PBMCs) of 29 patients and donors were cultured in CellGro SCGM with IL-2 and OKT3 antibody to expand the NK cell fraction. The killer cell immunoglobulin-like receptor (KIR) and HLA repertoire were determined by sequence specific priming and sequence based typing respectively. The percentage of NK cell expansion from the total PBMC fraction varied between 5.4% and 71.6%. A significantly better NK cell expansion was observed for individuals homozygous for HLA-C epitope group 2 (p<0.05). For evaluation of cytolytic competence of the cultured NK cells, specific killing of an HLA class I expression deficient LCL 721.221 cell line and three 721.221 cell lines transfected with different HLA-C alleles was determined. A significantly better NK cell-induced specific cytotoxicity was observed towards the untransfected 721.221 cells compared to the HLA-C transfected 721.221 cells. No significant differences were observed between killing of the three HLA-C transfected 721.221 cell lines. We have shown that cytolytic capacities of the cultured NK cells are maintained and in vitro expansion of NK cells is dependant on the presence of HLA-C alleles.

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Abi-Rached, Laurent, and Peter Parham. "Natural selection drives recurrent formation of activating killer cell immunoglobulin-like receptor and Ly49 from inhibitory homologues." Journal of Experimental Medicine 201, no. 8 (April 18, 2005): 1319–32. http://dx.doi.org/10.1084/jem.20042558.

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Expression of killer cell Ig-like receptors (KIRs) diversifies human natural killer cell populations and T cell subpopulations. Whereas the major histocompatibility complex class I binding functions of inhibitory KIR are known, specificities for the activating receptors have resisted analysis. To understand better activating KIR and their relationship to inhibitory KIR, we took the approach of reconstructing their natural history and that of Ly49, the analogous system in rodents. A general principle is that inhibitory receptors are ancestral, the activating receptors having evolved from them by mutation. This evolutionary process of functional switch occurs independently in different species to yield activating KIR and Ly49 genes with similar signaling domains. Selecting such convergent evolution were the signaling adaptors, which are older and more conserved than any KIR or Ly49. After functional shift, further activating receptors form through recombination and gene duplication. Activating receptors are short lived and evolved recurrently, showing they are subject to conflicting selections, consistent with activating KIR's association with resistance to infection, reproductive success, and susceptibility to autoimmunity. Our analysis suggests a two-stage model in which activating KIR or Ly49 are initially subject to positive selection that rapidly increases their frequency, followed by negative selection that decreases their frequency and leads eventually to loss.

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Lu, C., Y. J. Shen, Y. F. Deng, C. Y. Wang, G. Fan, Y. Q. Liu, S. M. Zhao, et al. "Association of killer cell immunoglobulin-like receptors with pulmonary tuberculosis in Chinese Han." Genetics and Molecular Research 11, no. 2 (2012): 1370–78. http://dx.doi.org/10.4238/2012.may.15.7.

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50

Sosnina, K., D. Zastavna, O. Terpyliak, L. Bober, and H. Makukh. "P004 Killer Cell Immunoglobulin-like Receptors (KIR) genes repertoire among cystic fibrosis patients." Journal of Cystic Fibrosis 18 (June 2019): S57—S58. http://dx.doi.org/10.1016/s1569-1993(19)30299-1.

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