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https://www.readbyqxmd.com/read/28521443/loss-of-fas-expression-and-high-expression-of-hla-e-promoting-the-immune-escape-of-early-colorectal-cancer-cells
#1
Renxiang Huang, Dongyang Zhang, Feng Li, Zili Xiao, Meiling Wu, Dongyun Shi, Ping Xiang, Zhijun Bao
Previous studies have investigated the mechanisms of immune evasion of tumor cells in numerous types of advanced solid malignant tumor, and several types of immune preparations have been administered as antitumor adjuvant therapies. However, in the majority of studies, the efficacy of therapies has been revealed to be limited. The present study aimed to investigate the immune evasion mechanisms employed by early colorectal cancer cells and the expression of the molecules associated with immune evasion during the malignant transformation process of normal colorectal epithelial cells to measure the effects of immune intervention for early colorectal cancer, and to improve the efficacy of immunotherapy...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28504668/hla-e-expressing-pluripotent-stem-cells-escape-allogeneic-responses-and-lysis-by-nk-cells
#2
Germán G Gornalusse, Roli K Hirata, Sarah E Funk, Laura Riolobos, Vanda S Lopes, Gabriel Manske, Donna Prunkard, Aric G Colunga, Laïla-Aïcha Hanafi, Dennis O Clegg, Cameron Turtle, David W Russell
Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the rejection of pluripotent stem cell (PSC)-derived products in allogeneic recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface expression of all class I molecules, but leaves the cells vulnerable to lysis by natural killer (NK) cells. Here we show that this 'missing-self' response can be prevented by forced expression of minimally polymorphic HLA-E molecules. We use adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the B2M locus in human PSCs in a manner that confers inducible, regulated, surface expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M and a peptide antigen), without surface expression of HLA-A, B or C...
May 15, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28475642/mhc-ib-molecule-qa-1-presents-mycobacterium-tuberculosis-peptide-antigens-to-cd8-t-cells-and-contributes-to-protection-against-infection
#3
Yao Bian, Shaobin Shang, Sarah Siddiqui, Jie Zhao, Simone A Joosten, Tom H M Ottenhoff, Harvey Cantor, Chyung-Ru Wang
A number of nonclassical MHC Ib molecules recognizing distinct microbial antigens have been implicated in the immune response to Mycobacterium tuberculosis (Mtb). HLA-E has been identified to present numerous Mtb peptides to CD8+ T cells, with multiple HLA-E-restricted cytotoxic T lymphocyte (CTL) and regulatory T cell lines isolated from patients with active and latent tuberculosis (TB). In other disease models, HLA-E and its mouse homolog Qa-1 can act as antigen presenting molecules as well as regulators of the immune response...
May 5, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28425192/soluble-hla-e-a-follow-up-biomarker-in-takayasu-arteritis-independent-of-hla-e-genotype
#4
Ruchika Goel, Jayakanthan Kabeerdoss, Hindhumathi Mohan, Sumita Danda, Visali Jayaseelan, T Sathish Kumar, John Jude, Paul Bacon, George Joseph, Debashish Danda
AIM: Disease activity assessment in Takayasu arteritis (TA) is challenging. Human leukocyte antigen E (HLA-E) is shed from endothelium into serum as a soluble molecule (sHLA-E) in response to inflammation. We aimed to study: (i) utility of sHLA-E as a biomarker of disease activity; and (ii) association of HLA-E polymorphism rs1264457 with clinical disease in Asian-Indian TA patients. MATERIALS AND METHODS: In phase-1, sHLA-E levels were estimated in sera of 50 consecutive TA patients at baseline visit and 27 healthy controls...
April 19, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28340094/nlrp2-is-a-suppressor-of-nf-%C3%A6-b-signaling-and-hla-c-expression-in-human-trophoblasts%C3%A2-%C3%A2
#5
Tamara Tilburgs, Torsten B Meissner, Leonardo M R Ferreira, Arend Mulder, Kiran Musunuru, Junqiang Ye, Jack L Strominger
During pregnancy, fetal extravillous trophoblasts (EVT) play a key role in the regulation of maternal T cell and NK cell responses. EVT display a unique combination of human leukocyte antigens (HLA); EVT do not express HLA-A and HLA-B, but do express HLA-C, HLA-E, and HLA-G. The mechanisms establishing this unique HLA expression pattern have not been fully elucidated. The major histocompatibility complex (MHC) class I and class II transcriptional activators NLRC5 and CIITA are expressed neither by EVT nor by the EVT model cell line JEG3, which has an MHC expression pattern identical to that of EVT...
April 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28337381/hla-e-inhibitor-enhances-the-killing-of-neuroblastoma-stem-cells-by-co-cultured-dendritic-cells-and-cytokine-induced-killer-cells-loaded-with-membrane-based-microparticles
#6
Zijun Zhen, Kaibin Yang, Litong Ye, Zhiyao You, Rirong Chen, Ying Liu, Youjian He
Neuroblastoma stem cells (NSCs) can cause drug resistance and tumor recurrence. This study aimed to enhance the lytic effect of dendritic cells (DCs) co-cultured with cytokine-induced killer (CIK) cells. NSCs were obtained by suspension culture, and DC-CIK cells were loaded with extracted NSC membrane-based microparticles (MMPs) before evaluating the lytic effect of DC-CIK cells on NSCs. After inhibiting the function or expression of human leukocyte antigen-E (HLA-E) in NSCs by anti-HLA-E monoclonal antibody or siRNA, the DC-CIK cell lytic effect on NSCs was re-assessed...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28299193/recent-advances-in-major-histocompatibility-complex-mhc-class-i-antigen-presentation-plastic-mhc-molecules-and-tapbpr-mediated-quality-control
#7
REVIEW
Andy van Hateren, Alistair Bailey, Tim Elliott
We have known since the late 1980s that the function of classical major histocompatibility complex (MHC) class I molecules is to bind peptides and display them at the cell surface to cytotoxic T cells. Recognition by these sentinels of the immune system can lead to the destruction of the presenting cell, thus protecting the host from pathogens and cancer. Classical MHC class I molecules (MHC I hereafter) are co-dominantly expressed, polygenic, and exceptionally polymorphic and have significant sequence diversity...
2017: F1000Research
https://www.readbyqxmd.com/read/28258595/transgenic-expression-of-human-leukocyte-antigen-e-attenuates-galko-hcd46-porcine-lung-xenograft-injury
#8
Christopher T Laird, Lars Burdorf, Beth M French, Natalia Kubicki, Xiangfei Cheng, Gheorghe Braileanu, Wenji Sun, Natalie A O'Neill, Arielle Cimeno, Dawn Parsell, Edward So, Andrea Bähr, Nikolai Klymiuk, Carol J Phelps, David Ayares, Agnes M Azimzadeh, Richard N Pierson
BACKGROUND: Lung xenografts remain susceptible to loss of vascular barrier function within hours in spite of significant incremental advances based on genetic engineering to remove the Gal 1,3-αGal antigen (GalTKO) and express human membrane cofactor protein (hCD46). Natural killer cells rapidly disappear from the blood during perfusion of GalTKO.hCD46 porcine lungs with human blood and presumably are sequestered within the lung vasculature. Here we asked whether porcine expression of the human NK cell inhibitory ligand HLA-E and β2 microglobulin inhibits GalTKO...
March 3, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28244222/a-novel-hla-e-allele-hla-e-01-01-01-07-identified-in-a-chinese-leukemia-patient
#9
S-X Wang, Y-P Xu, Li-M He
A novel HLA-E allele, HLA-E*01:01:01:07, was identified in a Chinese leukemia patient.
May 2017: HLA
https://www.readbyqxmd.com/read/28205421/a-novel-hla-e-allele-hla-e-01-01-01-06-identified-in-a-chinese-leukemia-patient
#10
Y-P Xu, S-X Wang, W-X Hong
A novel HLA-E allele, HLA-E*01:01:01:06, was identified in a Chinese leukemia patient.
April 2017: HLA
https://www.readbyqxmd.com/read/28197391/high-nkg2a-expression-contributes-to-nk-cell-exhaustion-and-predicts-a-poor-prognosis-of-patients-with-liver-cancer
#11
Cheng Sun, Jing Xu, Qiang Huang, Mei Huang, Hao Wen, Chuanshan Zhang, Jinyu Wang, Jiaxi Song, Meijuan Zheng, Haoyu Sun, Haiming Wei, Weihua Xiao, Rui Sun, Zhigang Tian
Background and Aims: As the predominant lymphocyte subset in the liver, natural killer (NK) cells have been shown to be highly associated with the outcomes of patients with chronic hepatitis B virus infection (CHB) and hepatocellular carcinoma (HCC). Previously, we reported that NKG2A, a checkpoint candidate, mediates human and murine NK cell dysfunction in CHB. However, NK cell exhaustion and, particularly, the level of NKG2A expression within liver tumors have not been reported. Methods: In this study, we analyzed NKG2A expression and the related dysfunction of NK cells located in intra- or peritumor regions of liver tissue samples from 207 HCC patients, in addition to analyzing disease outcomes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28185362/definitive-class-i-human-leukocyte-antigen-expression-in-gestational-placentation-hla-f-hla-e-hla-c-and-hla-g-in-extravillous-trophoblast-invasion-on-placentation-pregnancy-and-parturition
#12
Rinat Hackmon, Lakmini Pinnaduwage, Jianhong Zhang, Stephen J Lye, Daniel E Geraghty, Caroline E Dunk
PROBLEM: The extravillous trophoblasts (EVT) express HLA-C and HLA-G, but HLA-E and HLA-F are the subject of conflicting reports. In this study, we define the HLA expression profile during active EVT placental implantation, pregnancy development, and parturition. METHOD OF STUDY: Immunohistochemistry, q-PCR, and Western blot were used to investigate HLA-C, HLA-E, and HLA-F placental expression across gestation from the early first trimester, late first trimester, second trimester (n=10 in each), preterm gestation (n=6) to elective term cesarean section and term vaginal deliveries (n=12, 38-41 weeks)...
February 10, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28159587/evaluation-of-hla-g-hla-e-and-pd-l1-proteins-in-oral-osteosarcomas
#13
Diego Antonio Costa Arantes, Andréia Souza Gonçalves, Bruno Correia Jham, Eliza Carla Barroso Duarte, Élbio Candido de Paula, Henrique Moura de Paula, Elismauro Francisco Mendonça, Aline Carvalho Batista
OBJECTIVE: The aim of this study was to investigate the expression of human leukocyte antigens (HLAs) G and E and programmed death-ligand 1 (PD-L1) in oral osteosarcoma (OO) (n = 13). The relationship between the expression of these molecules and histologic grading and metastasis was also evaluated. STUDY DESIGN: HLA-G, HLA-E, and PD-L1 were identified by immunohistochemistry. Samples of normal bone tissue (n = 6) were used as controls. The sections were evaluated using a semiquantitative scoring system with an immunoreactive score, where a score of 0 was considered absent, ≤2 was low, and >2 was high expression...
December 14, 2016: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/28127896/new-insights-in-hla-e-polymorphism-by-refined-analysis-of-the-full-length-gene
#14
T I Olieslagers, C E M Voorter, M Groeneweg, Y Xu, L Wieten, M G J Tilanus
BACKGROUND: Human leukocyte antigen (HLA)-E is a non-classical HLA class I molecule that plays a role in both the innate and the adaptive immune response through interaction with receptors on natural killer- and T-cells. The HLA-E gene is characterized by limited polymorphism compared with the classical HLA loci on chromosome 6. At the start of this study, only 13 variable sites had been identified (IPD-IMGT/HLA Database v3.18.0). While most previous studies focused on polymorphism in exons 2 and 3 or specific gene regions, polymorphism in the other exons and introns could influence protein expression and function as well...
January 27, 2017: HLA
https://www.readbyqxmd.com/read/28012452/expression-of-hla-e-molecules-in-the-placental-tissue-of-women-infected-with-hiv-1-and-uninfected-women
#15
Juliana Martinez, Mariana Rodrigues Santiago, Gustavo Martelli-Palomino, Diego Agra de Souza, Társia Giabardo Alves Silva, Gyl Eanes Barros Silva, Fernando Chahud, Eduardo Antônio Donadi, Ana Paula Morais Fernandes
INTRODUCTION: Expression of HLA-E molecule in the placental extravillous trophoblast is associated with immune system cell inhibition, resulting in immune tolerance to fetus during pregnancy. HIV-1 can infect trophoblast cells and modify the expression of HLA-E, which may inhibit the cytotoxic activity of the immune system. AIM: The aim of this study was to evaluate HLA-E expression in third trimester placental tissue of women infected with HIV-1 and uninfected women...
January 2017: Placenta
https://www.readbyqxmd.com/read/27907087/prenylated-polyphenols-from-clusiaceae-and-calophyllaceae-with-immunomodulatory-activity-on-endothelial-cells
#16
Caroline Rouger, Sylvain Pagie, Séverine Derbré, Anne-Marie Le Ray, Pascal Richomme, Béatrice Charreau
Endothelial cells (ECs) are key players in inflammation and immune responses involved in numerous pathologies. Although attempts were experimentally undertaken to prevent and control EC activation, drug leads and probes still remain necessary. Natural products (NPs) from Clusiaceous and Calophyllaceous plants were previously reported as potential candidates to prevent endothelial dysfunction. The present study aimed to identify more precisely the molecular scaffolds that could limit EC activation. Here, 13 polyphenols belonging to 5 different chemical types of secondary metabolites (i...
2016: PloS One
https://www.readbyqxmd.com/read/27895918/classical-and-non-classical-hla-class-i-aberrations-in-primary-cervical-squamous-and-adenocarcinomas-and-paired-lymph-node-metastases
#17
Debbie M Ferns, A Marijne Heeren, Sanne Samuels, Maaike C G Bleeker, Tanja D de Gruijl, Gemma G Kenter, Ekaterina S Jordanova
BACKGROUND: Tumors avoid destruction by cytotoxic T cells (CTL) and natural killer (NK) cells by downregulation of classical human leukocyte antigens (HLA) and overexpression of non-classical HLA. This is the first study to investigate HLA expression in relation to histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC)), clinicopathological parameters and survival in a large cervical cancer patient cohort. METHODS: Classical (HLA-A and HLA-B/C)- and non-classical HLA molecules (HLA-E and HLA-G) were studied on primary tumors and paired lymph node (LN) metastases from cervical cancer patients (n = 136) by immunohistochemistry...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27871782/association-of-high-hla-e-expression-during-acute-cellular-rejection-and-numbers-of-hla-class-i-leader-peptide-mismatches-with-reduced-renal-allograft-survival
#18
Hana Guberina, Vera Rebmann, Bettina Wagner, Fabiola da Silva Nardi, Phillip Dziallas, Sebastian Dolff, Anja Bienholz, Jeremias Wohlschlaeger, Agnes Bankfalvi, Falko M Heinemann, Oliver Witzke, Yvonne M Zoet, Frans H J Claas, Peter A Horn, Andreas Kribben, Ilias I N Doxiadis
Non-classical Human Leukocyte Antigen (HLA)-E preferentially presents leader peptides derived from classical HLA-class I molecules. HLA-E can trigger opposed immune responses by interacting with inhibitory NKG2A or by activating NKG2C receptors on NK and T-cells. We studied the impact of HLA-E on renal allograft survival during acute cellular rejection. HLA-E expression was up-regulated in acute cellular rejection (ACR) biopsies (n=12) compared to biopsies from 13 renal allografts with no rejection-signs. HLA-E up-regulation was correlated with numbers of HLA-class I leader peptide mismatches (p=0...
November 4, 2016: Immunobiology
https://www.readbyqxmd.com/read/27868107/class-i-hla-haplotypes-form-two-schools-that-educate-nk-cells-in-different-ways
#19
Amir Horowitz, Zakia Djaoud, Neda Nemat-Gorgani, Jeroen Blokhuis, Hugo G Hilton, Vivien Béziat, Karl-Johan Malmberg, Paul J Norman, Lisbeth A Guethlein, Peter Parham
Natural killer (NK) cells are lymphocytes having vital functions in innate and adaptive immunity, as well as placental reproduction. Controlling education and functional activity of human NK cells are various receptors that recognize HLA class I on the surface of tissue cells. Epitopes of polymorphic HLA-A,-B and -C are recognized by equally diverse killer cell immunoglobulin-like receptors (KIR). In addition, a peptide cleaved from the leader sequence of HLA-A,-B or -C must bind to HLA-E for it to become a ligand for the conserved CD94:NKG2A receptor...
September 2016: Science Immunology
https://www.readbyqxmd.com/read/27859015/hla-e-allelic-genotype-correlates-with-hla-e-plasma-levels-and-predicts-early-progression-in-chronic-lymphocytic-leukemia
#20
Bettina Wagner, Fabiola da Silva Nardi, Sabine Schramm, Thomas Kraemer, Alexander A Celik, Jan Dürig, Peter A Horn, Ulrich Dührsen, Holger Nückel, Vera Rebmann
BACKGROUND: Human leukocyte antigen-E (HLA-E) is a nonclassical major histocompatibility complex class I molecule that recently came into sharper focus as a putative marker of advanced tumor stages and disease progression. In solid tumors, increased HLA-E expression as well as elevated soluble HLA-E (sHLA-E) plasma levels are associated with a poor prognosis; however, a role for HLA-E in hematologic malignancies remains to be established. METHODS: The authors analyzed HLA-E alleles and sHLA-E levels in a cohort of 110 individuals with chronic lymphocytic leukemia (CLL)...
November 2, 2016: Cancer
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