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https://www.readbyqxmd.com/read/29453317/histone-h3-3k27m-mobilizes-multiple-cancer-testis-ct-antigens-in-pediatric-glioma
#1
Houliang Deng, Jianming Zeng, Ting Zhang, Longcai Gong, Hongjie Zhang, Edwin Cheung, Chris Jones, Gang Li
Lysine to Methionine mutations at position 27 (K27M) in the histone H3 (H3.3 and H3.1) are highly prevalent in pediatric high-grade gliomas (HGG) that arise in the midline of the central nervous system. H3K27M perturbs the activity of polycomb repressor complex 2 (PRC2) and correlates with DNA hypomethylation; however, the pathways whereby H3K27M drive the development of pediatric HGG remain poorly understood. To understand the mechanism of pediatric HGG development driven by H3.3K27M and discover potential therapeutic targets or biomarkers, we established pediatric glioma cell model systems harboring H3...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29444931/complete-remission-with-reduction-of-high-risk-clones-following-haploidentical-nk-cell-therapy-against-mds-and-aml
#2
Andreas T Björklund, Mattias Carlsten, Ebba Sohlberg, Lisa L Liu, Trevor Clancy, Mohsen Karimi, Sarah Cooley, Jeffrey S Miller, Monika Klimkowska, Marie Schaffer, Emma Watz, Kristina I Wikstrom, Pontus Blomberg, Bjorn E Wahlin, Marzia Palma, Lotta Hansson, Per Ljungman, Eva Hellström-Lindberg, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
PURPOSE: To evaluate the safety, efficacy and immunobiological correlates of allogeneic NK cell-based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and de novo AML patients. EXPERIMENTAL DESIGN: Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy with IL-2-activated haploidentical NK cells. RESULTS: NK cell infusions were well tolerated with only transient adverse events observed in the 16 patients...
February 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29422902/t-cells-engaging-the-conserved-mhc-class-ib-molecule-qa-1b-with-tap-independent-peptides-are-semi-invariant-lymphocytes
#3
Elien M Doorduijn, Marjolein Sluijter, Bianca J Querido, Ursula J E Seidel, Claudia C Oliveira, Sjoerd H van der Burg, Thorbald van Hall
The HLA-E homolog in the mouse (Qa-1b) is a conserved MHC class Ib molecule presenting monomorphic peptides to germline-encoded natural killer receptor CD94/NKG2A. Previously, we demonstrated the replacement of this canonical peptide by a diverse peptidome upon deficiency of the TAP peptide transporter. Analysis of this Qa-1b-restricted T cell repertoire against these non-mutated neoantigens revealed characteristics of conventional hypervariable CD8+ T cells, but also of invariant T cell receptor (TCR)αβ T cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29394121/genetics-of-natural-killer-cells-in-human-health-disease-and-survival
#4
Peter Parham, Lisbeth A Guethlein
Natural killer (NK) cells have vital functions in human immunity and reproduction. In the innate and adaptive immune responses to infection, particularly by viruses, NK cells respond by secreting inflammatory cytokines and killing infected cells. In reproduction, NK cells are critical for genesis of the placenta, the organ that controls the supply of oxygen and nutrients to the growing fetus. Controlling NK cell functions are interactions of HLA class I with inhibitory NK cell receptors. First evolved was the conserved interaction of HLA-E with CD94:NKG2A; later established were diverse interactions of HLA-A, -B, -C with killer cell immunoglobulin-like receptors...
February 2, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29354360/human-leukocyte-antigen-hla-f-polymorphism-is-associated-with-chronic-hbv-infection
#5
Ahmed Baligh Laaribi, Naila Hannachi, Hamza Ben Yahia, Manal Marzouk, Asma Mehri, Manel Belhadj, Salwa Yacoub, Amel Letaief, Hadda-Imene Ouzari, Abdellatif Boudabous, Jalel Boukadida, Roberta Rizzo, Inès Zidi
Human leukocyte antigen (HLA)-F has been involved in immune regulation of infectious diseases. However, the role of HLA-F polymorphisms in hepatitis B infection outcomes remains unclear. Here, we aimed to determine HLA-F polymorphism implication in chronic HBV. Genotype analysis was performed for three single nucleotide polymorphisms (SNPs) of HLA-F and one SNP of HLA-E using PCR-SSP, in 252 Tunisian patients with chronic HBV infection stratified according to their HBV DNA levels (140 patients with low HBV DNA levels < 2000 IU/mL and 112 patients with high HBV DNA levels ≥ 2000 IU/mL) and 240 healthy controls (CTRL)...
January 2018: 3 Biotech
https://www.readbyqxmd.com/read/29302013/elevated-hla-a-expression-impairs-hiv-control-through-inhibition-of-nkg2a-expressing-cells
#6
Veron Ramsuran, Vivek Naranbhai, Amir Horowitz, Ying Qi, Maureen P Martin, Yuko Yuki, Xiaojiang Gao, Victoria Walker-Sperling, Gregory Q Del Prete, Douglas K Schneider, Jeffrey D Lifson, Jacques Fellay, Steven G Deeks, Jeffrey N Martin, James J Goedert, Steven M Wolinsky, Nelson L Michael, Gregory D Kirk, Susan Buchbinder, David Haas, Thumbi Ndung'u, Philip Goulder, Peter Parham, Bruce D Walker, Jonathan M Carlson, Mary Carrington
The highly polymorphic human leukocyte antigen (HLA) locus encodes cell surface proteins that are critical for immunity. HLA-A expression levels vary in an allele-dependent manner, diversifying allele-specific effects beyond peptide-binding preference. Analysis of 9763 HIV-infected individuals from 21 cohorts shows that higher HLA-A levels confer poorer control of HIV. Elevated HLA-A expression provides enhanced levels of an HLA-A-derived signal peptide that specifically binds and determines expression levels of HLA-E, the ligand for the inhibitory NKG2A natural killer (NK) cell receptor...
January 5, 2018: Science
https://www.readbyqxmd.com/read/29286392/overlapping-peptide-library-to-map-qa-1-epitopes-in-a-protein
#7
Yi Xu, Samiksha Wasnik, David J Baylink, Edmundo Carreon Berumen, Xiaolei Tang
Qa-1 (HLA-E in human) belongs to a group of non-classical major histocompatibility complex 1b (MHC-Ib) molecules. Recent data suggest that Qa-1 molecules play important roles in surveying cells for structural and functional integrity, inducing immune regulation, and limiting immune responses to viral infections. Additionally, functional augmentation of Qa-1-restricted CD8+ T cells through epitope immunization has shown therapeutic effects in several autoimmune disease animal models, e.g. experimental allergic encephalomyelitis, collagen-induced arthritis, and non-obese diabetes...
December 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29273955/prognostic-value-of-tumor-stroma-ratio-combined-with-the-immune-status-of-tumors-in-invasive-breast-carcinoma
#8
K M H Vangangelt, G W van Pelt, C C Engels, H Putter, G J Liefers, V T H B M Smit, R A E M Tollenaar, P J K Kuppen, W E Mesker
PURPOSE: Complex interactions occur between cancer cells and cells in the tumor microenvironment. In this study, the prognostic value of the interplay between tumor-stroma ratio (TSR) and the immune status of tumors in breast cancer patients was evaluated. METHODS: A cohort of 574 breast cancer patients was analyzed. The percentage of tumor stroma was visually estimated on Hematoxylin and Eosin (H&E) stained histological tumor tissue sections. Immunohistochemical staining was performed for classical human leukocyte antigen (HLA) class I, HLA-E, HLA-G, markers for regulatory T (Treg) cells, natural killer (NK) cells and cytotoxic T-lymphocytes (CTLs)...
December 22, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29228302/susceptibility-of-hla-e-01-03-allele-carriers-to-develop-cytomegalovirus-replication-after-living-donor-kidney-transplantation
#9
Hana Guberina, Fabiola da Silva Nardi, Rafael Tomoya Michita, Sebastian Dolff, Anja Bienholz, Falko M Heinemann, Benjamin Wilde, Mirko Trilling, Peter A Horn, Andreas Kribben, Oliver Witzke, Vera Rebmann
Cytomegalovirus (CMV) causes serious complications among solid-organ transplant recipients. We report the positive correlation between the presence of the Human Leukocyte Antigen (HLA)-E*01:03 allele in living-donor kidney recipients and CMV reactivation during the first year after transplantation. Thus, the HLA-E recipient genotyping may help to identify CMV-prone patients who require individualized patient-based CMV management.
December 8, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29184550/natural-killer-cell-interactions-with-classical-and-non-classical-human-leukocyte-antigen-class-i-in-hiv-1-infection
#10
REVIEW
Angelique Hölzemer, Wilfredo F Garcia-Beltran, Marcus Altfeld
Natural killer (NK) cells are effector lymphocytes of the innate immune system that are able to mount a multifaceted antiviral response within hours following infection. This is achieved through an array of cell surface receptors surveilling host cells for alterations in human leukocyte antigen class I (HLA-I) expression and other ligands as signs of viral infection, malignant transformation, and cellular stress. This interaction between HLA-I ligands and NK-cell receptor is not only important for recognition of diseased cells but also mediates tuning of NK-cell-effector functions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29176828/t-cell-recognition-of-mycobacterium-tuberculosis-peptides-presented-by-hla-e-derived-from-infected-human-cells
#11
Curtis McMurtrey, Melanie J Harriff, Gwendolyn M Swarbrick, Amanda Duncan, Meghan Cansler, Megan Null, Wilfried Bardet, Kenneth W Jackson, Deborah A Lewinsohn, William Hildebrand, David M Lewinsohn
HLA-E is a non-conventional MHC Class I molecule that has been recently demonstrated to present pathogen-derived ligands, resulting in the TCR-dependent activation of αβ CD8+ T cells. The goal of this study was to characterize the ligandome displayed by HLA-E following infection with Mycobacterium tuberculosis (Mtb) using an in-depth mass spectrometry approach. Here we identified 28 Mtb ligands derived from 13 different source proteins, including the Esx family of proteins. When tested for activity with CD8+ T cells isolated from sixteen donors, nine of the ligands elicited an IFN-γ response from at least one donor, with fourteen of 16 donors responding to the Rv0634A19-29 peptide...
2017: PloS One
https://www.readbyqxmd.com/read/29150562/the-role-of-mhc-e-in-t-cell-immunity-is-conserved-among-humans-rhesus-macaques-and-cynomolgus-macaques
#12
Helen L Wu, Roger W Wiseman, Colette M Hughes, Gabriela M Webb, Shaheed A Abdulhaqq, Benjamin N Bimber, Katherine B Hammond, Jason S Reed, Lina Gao, Benjamin J Burwitz, Justin M Greene, Fidel Ferrer, Alfred W Legasse, Michael K Axthelm, Byung S Park, Simon Brackenridge, Nicholas J Maness, Andrew J McMichael, Louis J Picker, David H O'Connor, Scott G Hansen, Jonah B Sacha
MHC-E is a highly conserved nonclassical MHC class Ib molecule that predominantly binds and presents MHC class Ia leader sequence-derived peptides for NK cell regulation. However, MHC-E also binds pathogen-derived peptide Ags for presentation to CD8(+) T cells. Given this role in adaptive immunity and its highly monomorphic nature in the human population, HLA-E is an attractive target for novel vaccine and immunotherapeutic modalities. Development of HLA-E-targeted therapies will require a physiologically relevant animal model that recapitulates HLA-E-restricted T cell biology...
November 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29124751/detailed-characterization-of-human-mycobacterium-tuberculosis-specific-hla-e-restricted-cd8-t-cells
#13
Teresa Prezzemolo, Krista E van Meijgaarden, Kees Lmc Franken, Nadia Caccamo, Francesco Dieli, Tom Hm Ottenhoff, Simone A Joosten
HLA-E presented antigens are interesting targets for vaccination given HLA-Es' essentially monomorphic nature. We have shown previously that Mycobacterium tuberculosis (Mtb) peptides are presented by HLA-E to CD8(+) effector T-cells, but the precise phenotype and functional capacity of these cells remains poorly characterized. We have developed and utilized in this study a new protocol combining HLA-E tetramer with intracellular staining for cytokines, transcription factors and cytotoxic molecules to characterize these cells in depth...
November 9, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29114247/elusive-role-of-the-cd94-nkg2c-nk-cell-receptor-in-the-response-to-cytomegalovirus-novel-experimental-observations-in-a-reporter-cell-system
#14
Aldi Pupuleku, Marcel Costa-García, Domènec Farré, Hartmut Hengel, Ana Angulo, Aura Muntasell, Miguel López-Botet
Human cytomegalovirus (HCMV) infection promotes the differentiation and persistent expansion of a mature NK cell subset, which displays high surface levels of the activating CD94/NKG2C NK cell receptor, together with additional distinctive phenotypic and functional features. The mechanisms underlying the development of adaptive NK cells remain uncertain but some observations support the involvement of a cognate interaction of CD94/NKG2C with ligand(s) displayed by HCMV-infected cells. To approach this issue, the heterodimer and its adaptor (DAP12) were expressed in the human Jurkat leukemia T cell line; signaling was detected by transfection of a reporter plasmid encoding for Luciferase (Luc) under NFAT/AP1-dependent control...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29098351/the-roles-of-genetic-factors-in-kawasaki-disease-a-systematic-review-and-meta-analysis-of-genetic-association-studies
#15
REVIEW
Xiaochuan Xie, Xiaohan Shi, Meilin Liu
This systematic review and meta-analysis aimed to better elucidate the roles of genetic factors in Kawasaki disease (KD), and determine the potential genetic biomarkers of KD. The systematic literature search of PubMed, Medline, Embase, Web of Science and CNKI identified 164 eligible studies. The qualitative synthesis revealed that 62 genes may be correlated with the susceptibility to KD, and 47 genes may be associated with the incidence of coronary artery lesions (CALs) in KD. A total of 53 polymorphisms in 34 genes were investigated in further quantitative synthesis...
November 2, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/29073617/preimplantation-factor-pif-promotes-hla-g-e-f-c-expression-in-jeg-3-choriocarcinoma-cells-and-endogenous-progesterone-activity
#16
Miya Soukaina Hakam, Jose Maria Miranda-Sayago, Soren Hayrabedyan, Krassimira Todorova, Patrick Simon Spencer, Asma Jabeen, Eytan R Barnea, Nelson Fernandez
BACKGROUND/AIMS: Pregnancy success requires mandatory maternal tolerance of the semi/ allogeneic embryo involving embryo-derived signals. Expression levels of PreImplantation Factor (PIF), a novel peptide secreted by viable embryos, correlate with embryo development, and its early detection in circulation correlates with a favourable pregnancy outcome. PIF enhances endometrial receptivity to promote embryo implantation. Via the p53 pathway, it increases trophoblast invasion, improving cell survival / immune privilege...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29059634/the-prognostic-benefit-of-tumour-infiltrating-natural-killer-cells-in-endometrial-cancer-is-dependent-on-concurrent-overexpression-of-human-leucocyte-antigen-e-in-the-tumour-microenvironment
#17
M A C Versluis, S Marchal, A Plat, G H de Bock, T van Hall, M de Bruyn, H Hollema, H W Nijman
BACKGROUND: Human Leucocyte Antigen- E (HLA-E) has been reported as both a positive and negative prognostic marker in cancer. This apparent discrepancy may be due to opposing actions of HLA-E on tumour-infiltrating immune cells. Therefore, we evaluated HLA-E expression and survival in relation to the presence of intratumoural natural killer (NK) cells and cytotoxic T cells (CTLs). METHODS: Tissue microarrays (TMAs) of endometrial tumours were used for immunohistochemical staining of parameters of interest...
October 20, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29057510/release-of-pig-leukocytes-and-reduced-human-nk-cell-recruitment-during-ex-vivo-perfusion-of-hla-e-human-cd46-double-transgenic-pig-limbs-with-human-blood
#18
Gisella Puga Yung, Anjan K Bongoni, Amandine Pradier, Natacha Madelon, Maria Papaserafeim, Riccardo Sfriso, David L Ayares, Eckhard Wolf, Nikolai Klymiuk, Andrea Bähr, Mihai A Constantinescu, Esther Voegelin, David Kiermeir, Hansjörg Jenni, Robert Rieben, Jörg D Seebach
BACKGROUND: In pig-to-human xenotransplantation, interactions between human natural killer (NK) cells and porcine endothelial cells (pEC) are characterized by recruitment and cytotoxicity. Protection from xenogeneic NK cytotoxicity can be achieved in vitro by the expression of the non-classical human leukocyte antigen-E (HLA-E) on pEC. Thus, the aim of this study was to analyze NK cell responses to vascularized xenografts using an ex vivo perfusion system of pig limbs with human blood...
October 22, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29023371/expression-profiles-of-ligands-for-activating-natural-killer-cell-receptors-on-hiv-infected-and-uninfected-cd4%C3%A2-%C2%BA-t-cells
#19
Alexandra Tremblay-McLean, Julie Bruneau, Bertrand Lebouché, Irene Lisovsky, Rujun Song, Nicole F Bernard
Natural Killer (NK) cell responses to HIV-infected CD4 T cells (iCD4) depend on the integration of signals received through inhibitory (iNKR) and activating NK receptors (aNKR). iCD4 activate NK cells to inhibit HIV replication. HIV infection-dependent changes in the human leukocyte antigen (HLA) ligands for iNKR on iCD4 are well documented. By contrast, less is known regarding the HIV infection related changes in ligands for aNKR on iCD4. We examined the aNKR ligand profiles HIV p24⁺ HIV iCD4s that maintained cell surface CD4 (iCD4⁺), did not maintain CD4 (iCD4(-)) and uninfected CD4 (unCD4) T cells for expression of unique long (UL)-16 binding proteins-1 (ULBP-1), ULBP-2/5/6, ULBP-3, major histocompatibility complex (MHC) class 1-related (MIC)-A, MIC-B, CD48, CD80, CD86, CD112, CD155, Intercellular adhesion molecule (ICAM)-1, ICAM-2, HLA-E, HLA-F, HLA-A2, HLA-C, and the ligands to NKp30, NKp44, NKp46, and killer immunoglobulin-like receptor 3DS1 (KIR3DS1) by flow cytometry on CD4 T cells from 17 HIV-1 seronegative donors activated and infected with HIV...
October 12, 2017: Viruses
https://www.readbyqxmd.com/read/28979268/nkg2c-nkg2a-natural-killer-cells-are-associated-with-a-lower-viral-set-point-and-may-predict-disease-progression-in-individuals-with-primary-hiv-infection
#20
Meichen Ma, Zhuo Wang, Xi Chen, Anfu Tao, Lei He, Shuai Fu, Zining Zhang, Yajing Fu, Chenxi Guo, Jing Liu, Xiaoxu Han, Junjie Xu, Zhenxing Chu, Haibo Ding, Hong Shang, Yongjun Jiang
Natural killer (NK) cells are the first line of defense against pathogens of the immune system and also play an important role in resistance against HIV. The activating receptor NKG2C and the inhibitory receptor NKG2A co-modulate the function of NK cells by recognizing the same ligand, HLA-E. However, the role of NKG2A and NKG2C on viral set point and the prediction of HIV disease progression have been rarely reported. In this study, we determined the expression of NKG2C or NKG2A on the surface of NK cells from 22 individuals with primary HIV infection (PHI) stage and 23 HIV-negative normal control (NC) subjects...
2017: Frontiers in Immunology
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