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https://www.readbyqxmd.com/read/28904123/unveiling-the-peptide-motifs-of-hla-c-and-hla-g-from-naturally-presented-peptides-and-generation-of-binding-prediction-matrices
#1
Moreno Di Marco, Heiko Schuster, Linus Backert, Michael Ghosh, Hans-Georg Rammensee, Stefan Stevanović
The classical HLA-C and the nonclassical HLA-E and HLA-G molecules play important roles both in the innate and adaptive immune system. Starting already during embryogenesis and continuing throughout our lives, these three Ags exert major functions in immune tolerance, defense against infections, and anticancer immune responses. Despite these important roles, identification and characterization of the peptides presented by these molecules has been lacking behind the more abundant HLA-A and HLA-B gene products...
September 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28899983/regulatory-nk-cells-mediated-between-immunosuppressive-monocytes-and-dysfunctional-t-cells-in-chronic-hbv-infection
#2
Haijun Li, Naicui Zhai, Zhongfeng Wang, Hongxiao Song, Yang Yang, An Cui, Tianyang Li, Guangyi Wang, Junqi Niu, Ian Nicholas Crispe, Lishan Su, Zhengkun Tu
BACKGROUND AND AIMS: HBV infection represents a major health problem worldwide, but the immunological mechanisms by which HBV causes chronic persistent infection remain only partly understood. Recently, cell subsets with suppressive features have been recognised among monocytes and natural killer (NK) cells. Here we examine the effects of HBV on monocytes and NK cells. METHODS: Monocytes and NK cells derived from chronic HBV-infected patients and healthy controls were purified and characterised for phenotype, gene expression and cytokines secretion by flow cytometry, quantitative real-time (qRT)-PCR, ELISA and western blotting...
September 12, 2017: Gut
https://www.readbyqxmd.com/read/28883078/hla-e-mismatch-is-associated-with-better-hematopoietic-stem-cell-transplantation-outcome-in-acute-leukemia-patients
#3
Chrysanthi Tsamadou, Daniel Fürst, Vladan Vucinic, Donald Bunjes, Christine Neuchel, Daphne Mytilineos, Martin Gramatzki, Renate Arnold, Eva Maria Wagner, Hermann Einsele, Carlheinz Müller, Hubert Schrezenmeier, Joannis Mytilineos
The immunomodulatory role of HLA-E in hematopoietic stem cell transplantation (HSCT) has not been yet extensively investigated. To this end we genotyped 509 10/10 HLA unrelated transplant pairs for HLA-E, in order to study the effect of HLA-E as NK-alloreactivity mediator on HSCT outcome in an acute leukemia setting. Overall survival (OS), disease free survival (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were set as endpoints. Analysis of our data revealed a significant correlation between HLA-E mismatch and improved HSCT outcome, as shown by both, univariate (53% vs 38%, p=0...
September 7, 2017: Haematologica
https://www.readbyqxmd.com/read/28882620/hla-class-ia-and-ib-molecules-and-foxp3-tils-in-relation-to-the-prognosis-of-malignant-melanoma-patients
#4
Wenna Nascimento Melsted, Lasse Lindholm Johansen, Jørgen Lock-Andersen, Nille Behrendt, Jens Ole Eriksen, Michael Bzorek, Thomas Scheike, Thomas Vauvert F Hviid
HLA class Ia (HLA-ABC) and HLA class Ib (HLA-E, -F and -G) molecules and FOXP3+ tumor-infiltrating lymphocytes (TILs) are often reported as relevant factors of tumor immune regulation. We investigated their expression as prognostic factors in 200 patients with primary cutaneous melanoma (PCM). In our cohort, patients with tumors showing upregulation of HLA-ABC molecules had significantly thicker tumors (32% vs 7%, P<0.001), frequent ulceration (20% vs 6%, P=0.007) and frequent nodular melanomas (20% vs 4%, P=0...
September 4, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28874155/the-regulation-of-ovary-and-conceptus-on-the-uterine-natural-killer-cells-during-early-pregnancy
#5
REVIEW
Han Gong, Yilu Chen, Jingjie Xu, Xingxing Xie, Dainan Yu, Bei Yang, Haibin Kuang
Uterine natural killer (uNK) cells are short-lived, terminally differentiated and the most abundant lymphocytes in the uterus which play a crucial role in the spiral arteriole modification and establishment of successful pregnancy. Dysregulation of uNK cells has been linked to gestational implications such as recurrent pregnancy loss, preeclampsia and fetal growth retardation. There is evidence showing that progesterone and estrogen can regulate the recruitment, proliferation, differentiation and function of uNK cells via direct action on intracellular nuclear receptors or through intermediary cells in the uterus during early pregnancy...
September 6, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28783683/class-i-hla-haplotypes-form-two-schools-that-educate-nk-cells-in-different-ways
#6
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 that have vital functions in innate and adaptive immunity, as well as placental reproduction. Polymorphic human leukocyte antigen (HLA) class I educates NK cells through interactions with killer cell immunoglobulin-like receptors (KIRs) and by supplying peptides that bind HLA-E to form ligands for CD94/NKG2A receptors on NK cells. HLA-B dimorphism in the leader peptide modulates this latter function: -21methionine (-21M) delivers functional peptides, but -21threonine (-21T) does not...
September 9, 2016: Science Immunology
https://www.readbyqxmd.com/read/28769934/human-leukocyte-antigen-hla-and-immune-regulation-how-do-classical-and-non-classical-hla-alleles-modulate-immune-response-to-human-immunodeficiency-virus-and-hepatitis-c-virus-infections
#7
REVIEW
Nicole B Crux, Shokrollah Elahi
The genetic factors associated with susceptibility or resistance to viral infections are likely to involve a sophisticated array of immune response. These genetic elements may modulate other biological factors that account for significant influence on the gene expression and/or protein function in the host. Among them, the role of the major histocompatibility complex in viral pathogenesis in particular human immunodeficiency virus (HIV) and hepatitis C virus (HCV), is very well documented. We, recently, added a novel insight into the field by identifying the molecular mechanism associated with the protective role of human leukocyte antigen (HLA)-B27/B57 CD8(+) T cells in the context of HIV-1 infection and why these alleles act as a double-edged sword protecting against viral infections but predisposing the host to autoimmune diseases...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28727628/replication-confirms-the-association-of-loci-in-foxe1-pde8b-capzb-and-pde10a-with-thyroid-traits-a-genetics-of-diabetes-audit-and-research-tayside-study-godarts
#8
Enrique Soto-Pedre, Moneeza K Siddiqui, Alex S Doney, Colin N A Palmer, Ewan R Pearson, Graham P Leese
OBJECTIVE: Replication of associations in genome-wide association studies is desirable to ensure that such signals are potentially clinically meaningful. This study aimed to replicate associations of selected single-nucleotide polymorphisms (SNPs) with hypothyroidism and serum thyroid-stimulating hormone (TSH) using electronic medical records (EMRs). PATIENTS AND METHODS: A cross-sectional study was carried out among patients of European Caucasian ethnicity from the Genetics of Diabetes Audit and Research Tayside recruited in Tayside (Scotland, UK)...
October 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28711734/immunohistochemical-investigations-on-the-expression-of-programmed-cell-death-ligand-1-human-leukocyte-antigens-g-and-e-and-granzyme-b-in-intraoral-mucoepidermoid-carcinoma
#9
Carla Mosconi, Diego Antônio Costa Arantes, Andréia Souza Gonçalves, Rita de Cássia Gonçalves Alencar, José Carlos Oliveira, Tarcília Aparecida Silva, Elismauro Francisco Mendonça, Aline Carvalho Batista
OBJECTIVE: To identify the expression of nonclassical human leukocyte antigen G and E (HLA-G and -E), programmed cell death ligand-1 (PD-L1) and granzyme B (GB) in intraoral mucoepidermoid carcinomas (MECs), and to assess whether such expressions are related to metastasis, survival, staging, tumor grade and number of GB-positive cells. DESIGN: For this cross-sectional study, samples of MEC (n=30) were selected and classified as low-grade (LG), intermediate-grade (IG) or high-grade (HG), according to the WHO grading system...
July 8, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28699111/hla-class-ib-in-pregnancy-and-pregnancy-related-disorders
#10
REVIEW
Gry Persson, Wenna Nascimento Melsted, Line Lynge Nilsson, Thomas Vauvert F Hviid
The HLA class Ib genes, HLA-E, HLA-F, and HLA-G, were discovered long after the classical HLA class Ia genes. The elucidation of their functions had a modest beginning. However, their basic functions and involvement in pathophysiology and a range of diseases are now emerging. Although results from a range of studies support the functional roles for the HLA class Ib molecules in adult life, especially HLA-G and HLA-F have most intensively been, and were also primarily, studied in relation to reproduction and pregnancy...
July 11, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28676677/hla-e-presents-glycopeptides-from-the-mycobacterium-tuberculosis-protein-mpt32-to-human-cd8-t-cells
#11
Melanie J Harriff, Lisa M Wolfe, Gwendolyn Swarbrick, Megan Null, Meghan E Cansler, Elizabeth T Canfield, Todd Vogt, Katelynne Gardner Toren, Wei Li, Mary Jackson, Deborah A Lewinsohn, Karen M Dobos, David M Lewinsohn
Infection with Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, remains a global health concern. Both classically and non-classically restricted cytotoxic CD8(+) T cells are important to the control of Mtb infection. We and others have demonstrated that the non-classical MHC I molecule HLA-E can present pathogen-derived peptides to CD8(+) T cells. In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8(+) T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28653491/the-role-of-%C3%AE-%C3%AE-t-cells-during-human-pregnancy
#12
Chunyu Huang, Yong Zeng, Wenwei Tu
Pregnancy is an evolutionarily important and mysterious process. The placenta, as the nutrient and gas exchange organ, plays an essential role during this process. In addition, the interaction between trophoblast and maternal immune cells at the maternal-fetal interface is also associated with successful pregnancy. Human leukocyte antigen (HLA) molecules on trophoblast cells are involved in protecting the fetus from maternal rejection. Trophoblast cells comprise three subpopulations, including syncytiotrophoblast cells, cytotrophoblast cells, and extravillous trophoblast cells, and these cells express different HLA molecules...
June 27, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28637877/ex-vivo-expanded-adaptive-nk-cells-effectively-kill-primary-acute-lymphoblastic-leukemia-cells
#13
Lisa L Liu, Vivien Béziat, Vincent Y S Oei, Aline Pfefferle, Marie Schaffer, Sören Lehmann, Eva Hellström-Lindberg, Stefan Söderhäll, Mats Heyman, Dan Grandér, Karl-Johan Malmberg
Manipulation of human natural killer (NK) cell repertoires promises more effective strategies for NK cell-based cancer immunotherapy. A subset of highly differentiated NK cells, termed adaptive NK cells, expands naturally in vivo in response to human cytomegalovirus (HCMV) infection, carries unique repertoires of inhibitory killer cell immunoglobulin-like receptors (KIR), and displays strong cytotoxicity against tumor cells. Here, we established a robust and scalable protocol for ex vivo generation and expansion of adaptive NK cells for cell therapy against pediatric acute lymphoblastic leukemia (ALL)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28634589/hla-class-ia-and-ib-polyreactive-anti-hla-e-igg2a-monoclonal-antibodies-tfl-006-and-tfl-007-suppress-anti-hla-igg-production-by-cd19-b-cells-and-proliferation-of-cd4-t-cells-while-upregulating-tregs
#14
REVIEW
Mepur H Ravindranath
The anti-HLA-E IgG2a mAbs, TFL-006 and TFL-007, reacted with all HLA-I antigens, similar to the therapeutic preparations of IVIg. Indeed, IVIg lost its HLA reactivity, when its HLA-E reactivity was adsorbed out. US-FDA approved IVIg to reduce antibodies in autoimmune diseases. But the mechanism underlying IVIg-mediated antibody reduction could not be ascertained due to the presence of other polyclonal antibodies. In spite of it, the cost prohibitive high or low IVIg is administered to patients waiting for donor organ and for allograft recipients for lowering antiallograft antibodies...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28623356/high-risk-human-papillomavirus-e7-alters-host-dna-methylome-and-represses-hla-e-expression-in-human-keratinocytes
#15
Louis Cicchini, Rachel Z Blumhagen, Joseph A Westrich, Mallory E Myers, Cody J Warren, Charlotte Siska, David Raben, Katerina J Kechris, Dohun Pyeon
Human papillomavirus (HPV) infection distinctly alters methylation patterns in HPV-associated cancer. We have recently reported that HPV E7-dependent promoter hypermethylation leads to downregulation of the chemokine CXCL14 and suppression of antitumor immune responses. To investigate the extent of gene expression dysregulated by HPV E7-induced DNA methylation, we analyzed parallel global gene expression and DNA methylation using normal immortalized keratinocyte lines, NIKS, NIKS-16, NIKS-18, and NIKS-16∆E7...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28576831/shifting-the-balance-of-activating-and-inhibitory-natural-killer-receptor-ligands-on-braf-v600e-melanoma-lines-with-vemurafenib
#16
Alexandra Frazao, Marina Colombo, Emmanuelle Fourmentraux-Neves, Meriem Messaoudene, Sylvie Rusakiewicz, Laurence Zitvogel, Eric Vivier, Frederic Vely, Florence Faure, Brigitte Dreno, Houssem Benlalam, Fanny Bouquet, Ariel Savina, Eric Pasmant, Antoine Toubert, Marie Francoise Avril, Anne Caignard
Over 60% of human melanoma tumors bear a mutation in the BRAF gene. The most frequent mutation is a substitution at codon 600 (V600E), leading to a constitutively active BRAF and overactivation of the mitogen-activated protein kinase (MAPK) pathway. Patients harboring mutated BRAF respond to kinase inhibitors such as vemurafenib. However, these responses are transient and relapses are frequent. Melanoma cells are efficiently lysed by activated natural killer (NK) cells. Melanoma cells express several stress-induced ligands that are recognized by activating NK cell receptors...
June 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28566275/fibroblast-adapted-human-cmv-vaccines-elicit-predominantly-conventional-cd8-t-cell-responses-in-humans
#17
Susan E Murray, Pavlo A Nesterenko, Adam L Vanarsdall, Michael W Munks, Savannah M Smart, Eren M Veziroglu, Lavinia C Sagario, Ronzo Lee, Frans H J Claas, Ilias I N Doxiadis, Michael A McVoy, Stuart P Adler, Ann B Hill
Cytomegalovirus (CMV)-based vaccines have shown remarkable efficacy in the rhesus macaque model of acquired immune deficiency syndrome, enabling 50% of vaccinated monkeys to clear a subsequent virulent simian immunodeficiency virus challenge. The protective vaccine elicited unconventional CD8 T cell responses that were entirely restricted by MHC II or the nonclassical MHC I molecule, MHC-E. These unconventional responses were only elicited by a fibroblast-adapted rhesus CMV vector with limited tissue tropism; a repaired vector with normal tropism elicited conventional responses...
July 3, 2017: Journal of Experimental Medicine
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
#18
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
#19
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...
August 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
#20
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 2017: PLoS Pathogens
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