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https://www.readbyqxmd.com/read/29610856/natural-killer-cell-inhibition-by-hla-e-molecules-on-induced-pluripotent-stem-cell-derived-retinal-pigment-epithelial-cells
#1
Sunao Sugita, Kenichi Makabe, Yuko Iwasaki, Shota Fujii, Masayo Takahashi
Purpose: To determine whether human induced pluripotent stem (iPS) cell-derived retinal pigment epithelial (RPE) cells (iPS-RPE) can suppress natural killer (NK) cell activation. Methods: iPS-RPE cells were cocultured with peripheral blood mononuclear cells (PBMCs) or purified NK cells from healthy donors after stimulation with cytokines. To confirm expression of NK cell-specific markers, flow cytometry and quantitative RT-PCR (qRT-PCR) were performed. NK cells (or PBMCs) cocultured with iPS-RPE cells were assessed for proliferation by Ki-67 expression with flow cytometry, and NK suppression by RPE cells was assessed for granzyme B production with ELISA...
April 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29587858/hla-and-proteasome-expression-body-map
#2
Sebastian Boegel, Martin Löwer, Thomas Bukur, Patrick Sorn, John C Castle, Ugur Sahin
BACKGROUND: The presentation of HLA peptide complexes to T cells is a highly regulated and tissue specific process involving multiple transcriptionally controlled cellular components. The extensive polymorphism of HLA genes and the complex composition of the proteasome make it difficult to map their expression profiles across tissues. METHODS: Here we applied a tailored gene quantification pipeline to 4323 publicly available RNA-Seq datasets representing 55 normal tissues and cell types to examine expression profiles of (classical and non-classical) HLA class I, class II and proteasomal genes...
March 27, 2018: BMC Medical Genomics
https://www.readbyqxmd.com/read/29562195/unconventional-t-cell-targets-for-cancer-immunotherapy
#3
REVIEW
Dale I Godfrey, Jérôme Le Nours, Daniel M Andrews, Adam P Uldrich, Jamie Rossjohn
Most studies on the immunotherapeutic potential of T cells have focused on CD8 and CD4 T cells that recognize peptide antigens (Ag) presented by polymorphic major histocompatibility complex (MHC) class I and MHC class II molecules, respectively. However, unconventional T cells, which interact with MHC class Ib and MHC-I like molecules, are also implicated in tumor immunity, although their role therein is unclear. These include unconventional T cells targeting MHC class Ib molecules such as HLA-E and its murine ortholog Qa-1b, natural killer T (NKT) cells, mucosal associated invariant T (MAIT) cells, and γδ T cells...
March 20, 2018: Immunity
https://www.readbyqxmd.com/read/29545802/potential-beneficial-effects-of-cytomegalovirus-infection-after-transplantation
#4
REVIEW
Nicolle H R Litjens, Lotte van der Wagen, Jurgen Kuball, Jaap Kwekkeboom
Cytomegalovirus (CMV) infection can cause significant complications after transplantation, but recent emerging data suggest that CMV may paradoxically also exert beneficial effects in two specific allogeneic transplant settings. These potential benefits have been underappreciated and are therefore highlighted in this review. First, after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) using T-cell and natural killer (NK) cell-replete grafts, CMV reactivation is associated with protection from leukemic relapse...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29536572/multiple-genetically-modified-gtko-hcd46-hla-e-h%C3%AE-2-mg-porcine-hearts-are-protected-from-complement-activation-and-natural-killer-cell-infiltration-during-ex-vivo-perfusion-with-human-blood
#5
Jan-Michael Abicht, Riccardo Sfriso, Bruno Reichart, Matthias Längin, Katja Gahle, Gisella L Puga Yung, Jörg D Seebach, Robert Rieben, David Ayares, Eckhard Wolf, Nikolai Klymiuk, Andrea Baehr, Alexander Kind, Tanja Mayr, Andreas Bauer
BACKGROUND: In pig-to-human xenotransplantation, early cellular rejection reactions are mediated by natural killer cells (NK cells). Human NK cells are inhibited by HLA-E via CD94/NKG2A receptors. To protect porcine grafts against human NK cell responses, transgenic GTKO pigs expressing hCD46 and HLA-E have been generated. The aim of this study was to test the effect of this genetic modification on xenogeneic, and in particular human NK cell response, using an ex vivo perfusion model of pig hearts with human blood...
March 14, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29514694/aberrant-stat-phosphorylation-signaling-in-peripheral-blood-mononuclear-cells-from-multiple-sclerosis-patients
#6
Ester Canto, Noriko Isobe, Alessandro Didonna, Stephen L Hauser, Jorge R Oksenberg
BACKGROUND: Multiple sclerosis (MS) is characterized by increased activation of peripheral blood mononuclear cells (PBMCs), linked to perturbations in the phosphorylation of signaling proteins. METHODS: We developed a phosphoflow cytometry protocol to assess the levels of 11 phosphorylated nuclear proteins at baseline conditions and after cell activation in distinct PBMC populations from 41 treatment-naïve relapsing-remitting (RR) MS subjects and 37 healthy controls, and in a second cohort of 9 untreated RRMS patients and 10 secondary progressive (SP) MS patients...
March 7, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29499226/clinicopathologic-significance-of-hla-g-and-hla-e-molecules-in-tunisian-patients-with-ovarian-carcinoma
#7
Wafa Babay, Hamza Ben Yahia, Nadia Boujelbene, Nour Zidi, Ahmed Baligh Laaribi, Dhikra Kacem, Radhia Ben Ghorbel, Abdellatif Boudabous, Hadda-Imene Ouzari, Roberta Rizzo, Vera Rebmann, Karima Mrad, Inès Zidi
BACKGROUND: The human leukocyte antigen (HLA)-G and HLA-E, non classical HLA class I molecules, have been highly implicated in immune tolerance. HLA-G and HLA-E molecules were proposed as putative markers of several advanced cancers. As a step towards a better understanding of ovarian carcinoma, we evaluated the expression of both HLA-G and HLA-E molecules and explored their prognostic implication. METHODS: HLA-G and HLA-E expression were studied by immunohistochemistry on ovarian carcinoma tissues...
February 27, 2018: Human Immunology
https://www.readbyqxmd.com/read/29491867/acquired-natural-killer-cell-dysfunction-in-the-tumor-microenvironment-of-classic-hodgkin-lymphoma
#8
REVIEW
Jodi Chiu, Daniel M Ernst, Armand Keating
An understanding of interactions within the tumor microenvironment (TME) of classic Hodgkin lymphoma (cHL) has helped pave the way to novel immunotherapies that have enabled dormant and tumor-tolerant immune cells to be reactivated. The immunosuppressive nature of the TME in cHL specifically inhibits the proliferation and activity of natural killer (NK) cells, which contributes to tumor immune-escape mechanisms. This deficiency of NK cells begins at the tumor site and progresses systemically in patients with advanced disease or adverse prognostic factors...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29459477/intrinsic-functional-potential-of-nk-cell-subsets-constrains-retargeting-driven-by-chimeric-antigen-receptors
#9
Vincent Yi Sheng Oei, Marta Siernicka, Agnieszka Graczyk-Jarzynka, Hanna Julie Hoel, Weiwen Yang, Daniel Palacios, Hilde Almåsbak, Malgorzata Bajor, Dennis Clement, Ludwig Brandt, Björn Önfelt, Jodie Goodridge, Magdalena Winiarska, Radoslaw Zagozdzon, Johanna Olweus, Jon-Amund Kyte, Karl-Johan Malmberg
Natural killer (NK) cells hold potential as a source of allogeneic cytotoxic effector cells for chimeric antigen receptor (CAR)-mediated therapies. Here, we explored the feasibility of transfecting CAR-encoding mRNA into primary NK cells and investigated how the intrinsic potential of discrete NK-cell subsets affects retargeting efficiency. After screening five second- and third-generation anti-CD19 CAR constructs with different signaling domains and spacer regions, a third-generation CAR with the CH2-domain removed was selected based on its expression and functional profiles...
February 19, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29453317/histone-h3-3k27m-mobilizes-multiple-cancer-testis-ct-antigens-in-pediatric-glioma
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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)...
April 2018: 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
#18
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
#19
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
#20
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
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