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https://www.readbyqxmd.com/read/27935327/activation-induced-cell-death-aicd-of-human-melanoma-antigen-specific-tcr-engineered-cd8-t-cells-involves-jnk-bim-and-p53
#1
Arvind Chhabra, Bijay Mukherji, Deepika Batra
OBJECTIVES: Adoptive cancer immunotherapy (ACT) with transgenic T cell receptor (TCR) engineered (TCReng) anti-tumor T cells has produced encouraging results, however, efficacy of these approaches need improvement. Since premature activation induced cell death (AICD) of adoptively administered T cells could be a major impediment, we examined the mechanism(s) underlying AICD in TCReng CD8+ cytolytic T lymphocytes (CTL). METHODS: AICD in human tumor antigen specific MHC class I restricted TCR engineered CD8+ CTL was induced by exposing them to cognate peptide epitope...
December 9, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27934901/towards-peptide-vaccines-against-zika-virus-immunoinformatics-combined-with-molecular-dynamics-simulations-to-predict-antigenic-epitopes-of-zika-viral-proteins
#2
Muhammad Usman Mirza, Shazia Rafique, Amjad Ali, Mobeen Munir, Nazia Ikram, Abdul Manan, Outi M H Salo-Ahen, Muhammad Idrees
The recent outbreak of Zika virus (ZIKV) infection in Brazil has developed to a global health concern due to its likely association with birth defects (primary microcephaly) and neurological complications. Consequently, there is an urgent need to develop a vaccine to prevent or a medicine to treat the infection. In this study, immunoinformatics approach was employed to predict antigenic epitopes of Zika viral proteins to aid in development of a peptide vaccine against ZIKV. Both linear and conformational B-cell epitopes as well as cytotoxic T-lymphocyte (CTL) epitopes were predicted for ZIKV Envelope (E), NS3 and NS5 proteins...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27932293/the-macroautophagy-machinery-in-endo-and-exocytosis
#3
REVIEW
Christian Münz
Macroautophagy and the autophagy related gene (Atg) machinery execute during their canonical function cytoplasmic constituent degradation in lysosomes. This canonical function contributes to pathogen restriction and intracellular antigen presentation on major histocompatibility complex (MHC) class II molecules to CD4(+) T cells. However, in recent years it has become clear that the Atg machinery is also used for other membrane transport functions, including endocytosis and exocytosis. This review describes these non-canonical functions in the context of antigen presentation on MHC class I and II molecules to CD8(+) and CD4(+) T cells, respectively, and during viral replication...
December 5, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27928884/building-proteomic-tool-boxes-to-monitor-mhc-class-i-and-class-ii-peptides
#4
REVIEW
Frances-Rose Schumacher, Lélia Delamarre, Suchit Jhunjhunwala, Zora Modrusan, Qui T Phung, Joshua E Elias, Jennie R Lill
Major histocompatibility complex Class I (MHCI) and Class II (MHCII) presented peptides powerfully modulate T cell immunity and play a vital role in generating effective anti-tumor and anti-viral immune responses in mammals. Characterizing these MHCI or MHCII presented peptides can help generate therapeutic treatments, afford information on T cell mediated biomarkers, provide insight into disease progression, and reduce adverse anti-drug side effects from engineered biotherapeutics. Here, we explore the tools and techniques commonly employed to discover both MHCI and MHCII presented peptides...
December 8, 2016: Proteomics
https://www.readbyqxmd.com/read/27915130/gamma-irradiation-enhanced-tollip-mediated-anti-inflammatory-action-through-structural-modification-of-quercetin-in-lipopolysaccharide-stimulated-macrophages
#5
Eui-Baek Byun, Beom-Su Jang, Hye-Min Kim, Mi-So Yang, Nak-Yun Sung, Eui-Hong Byun
The changes in molecular structure and anti-inflammatory action of a gamma-irradiated quercetin were examined. Quercetin was gamma-irradiated at doses of 0, 15, 30, 50, 100 and 150kGy, which induced new radiolytic peaks (the highest radiolytic peak at a dose of 30kGy). Treatment of intact- and gamma-irradiated quercetin did not induce a significant cellular toxicity of macrophages at concentrations ranging from 12.5 to 50μM. Treatment of LPS-stimulated macrophages with gamma-irradiated quercetin (30kGy) showed a higher inhibitory action than intact-quercetin groups in the excessive expression of inducible nitric oxide synthases-mediated nitric oxide, prostaglandin E2, pro-inflammatory cytokines level, such as tumor necrosis factor-α, interleukin-6 and interleukin-1β, reactive oxygen species, as well as cell surface molecules (CD80, CD86, and MHC class I/II)...
November 30, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27914923/alloantigen-gene-transfer-to-hepatocytes-promotes-tolerance-to-pancreatic-islet-graft-by-inducing-cd8-regulatory-t-cells
#6
Valentin Le Guen, Jean-Paul Judor, Françoise Boeffard, Vanessa Gauttier, Nicolas Ferry, Jean-Paul Soulillou, Sophie Brouard, Sophie Conchon
BACKGROUND & AIM: Induction of donor-specific immune tolerance is a good alternative to chronic life-long immunosuppression for transplant patients. Donor major histocompatibility complex (MHC) molecules represent the main targets of the allogeneic immune response of transplant recipients. Liver-targeted gene transfer with viral vectors induces tolerance toward the encoded antigen. The aim of this work was to determine whether alloantigen gene transfer to hepatocytes induces tolerance and promotes graft acceptance...
November 30, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27910927/novel-chemoimmunotherapeutic-strategy-for-hepatocellular-carcinoma-based-on-a-genome-wide-association-study
#7
Kaku Goto, Dorcas A Annan, Tomoko Morita, Wenwen Li, Ryosuke Muroyama, Yasuo Matsubara, Sayaka Ito, Ryo Nakagawa, Yasushi Tanoue, Masahisa Jinushi, Naoya Kato
Pharmacotherapeutic options are limited for hepatocellular carcinoma (HCC). Recently, we identified the anti-tumor ligand MHC class I polypeptide-related sequence A (MICA) gene as a susceptibility gene for hepatitis C virus-induced HCC in a genome-wide association study (GWAS). To prove the concept of HCC immunotherapy based on the results of a GWAS, in the present study, we searched for drugs that could restore MICA expression. A screen of the FDA-approved drug library identified the anti-cancer agent vorinostat as the strongest hit, suggesting histone deacetylase inhibitors (HDACis) as potent candidates...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909914/association-of-snp-variants-of-mhc-class-ii-drb-gene-with-thermo-physiological-traits-in-tropical-goats
#8
Abdulmojeed Yakubu, Adebowale E Salako, Marcos De Donato, Sunday O Peters, Michael I Takeet, Mathew Wheto, Moses Okpeku, Ikhide G Imumorin
Host defense in vertebrates depend on many secreted regulatory proteins such as major histocompatibility complex (MHC) class II which provide important regulatory and effector functions of T cells. Gene polymorphism in the second exon of Capra-DRB gene in three major Nigerian goat breeds [West African Dwarf (WAD), Red Sokoto (RS), and Sahel (SH)] was analyzed by restriction fragment length polymorphisms (RFLP). Four restriction enzymes, BsaHI, AluI, HaeIII, and SacII, were utilized. The association between the polymorphic sites and some heat tolerance traits were also investigated in a total of 70 WAD, 90 RS, and 50 SH goats...
December 1, 2016: Tropical Animal Health and Production
https://www.readbyqxmd.com/read/27907183/activation-of-innate-and-adaptive-immunity-by-a-recombinant-human-cytomegalovirus-strain-expressing-an-nkg2d-ligand
#9
Adriana Tomić, Pavankumar R Varanasi, Mijo Golemac, Suzana Malić, Peggy Riese, Eva M Borst, Eva Mischak-Weissinger, Carlos A Guzmán, Astrid Krmpotić, Stipan Jonjić, Martin Messerle
Development of an effective vaccine against human cytomegalovirus (HCMV) is a need of utmost medical importance. Generally, it is believed that a live attenuated vaccine would best provide protective immunity against this tenacious pathogen. Here, we propose a strategy for an HCMV vaccine that aims at the simultaneous activation of innate and adaptive immune responses. An HCMV strain expressing the host ligand ULBP2 for the NKG2D receptor was found to be susceptible to control by natural killer (NK) cells, and preserved the ability to stimulate HCMV-specific T cells...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27907087/prenylated-polyphenols-from-clusiaceae-and-calophyllaceae-with-immunomodulatory-activity-on-endothelial-cells
#10
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/27903740/protective-t-cell-responses-featured-by-concordant-recognition-of-middle-east-respiratory-syndrome-coronavirus-derived-cd8-t-cell-epitopes-and-host-mhc
#11
William J Liu, Jiaming Lan, Kefang Liu, Yao Deng, Yanfeng Yao, Shaolian Wu, Hong Chen, Lingling Bao, Haifeng Zhang, Min Zhao, Qihui Wang, Lingxia Han, Yan Chai, Jianxun Qi, Jincun Zhao, Songdong Meng, Chuan Qin, George F Gao, Wenjie Tan
The coordinated recognition of virus-derived T cell epitopes and MHC molecules by T cells plays a pivotal role in cellular immunity-mediated virus clearance. It has been demonstrated that the conformation of MHC class I (MHC I) molecules can be adjusted by the presented peptide, which impacts T cell activation. However, it is still largely unknown whether the conformational shift of MHC I influences the protective effect of virus-specific T cells. In this study, utilizing the Middle East respiratory syndrome coronavirus-infected mouse model, we observed that through the unusual secondary anchor Ile5, a CD8(+) T cell epitope drove the conformational fit of Trp(73) on the α1 helix of murine MHC I H-2K(d) In vitro renaturation and circular dichroism assays indicated that this shift of the structure did not influence the peptide/MHC I binding affinity...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27895179/thymic-dendritic-cell-subsets-display-distinct-efficiencies-and-mechanisms-of-intercellular-mhc-transfer
#12
Charles J Kroger, Nicholas A Spidale, Bo Wang, Roland Tisch
Thymic dendritic cells (DC) delete self-antigen-specific thymocytes, and drive development of Foxp3-expressing immunoregulatory T cells. Unlike medullary thymic epithelial cells, which express and present peripheral self-antigen, DC must acquire self-antigen to mediate thymic negative selection. One such mechanism entails the transfer of surface MHC-self peptide complexes from medullary thymic epithelial cells to thymic DC. Despite the importance of thymic DC cross-dressing in negative selection, the factors that regulate the process and the capacity of different thymic DC subsets to acquire MHC and stimulate thymocytes are poorly understood...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27894857/cytokine-induced-memory-like-differentiation-enhances-unlicensed-nk-cell-anti-leukemia-and-fc%C3%AE-riiia-triggered-responses
#13
Julia A Wagner, Melissa M Berrien-Elliott, Maximillian Rosario, Jeffrey W Leong, Brea A Jewell, Timothy Schappe, Sara Abdel-Latif, Todd A Fehniger
Cytokine-induced memory-like natural killer (NK) cells differentiate following short-term pre-activation with interleukin (IL)-12, IL-15, and IL-18 and display enhanced effector function in response to cytokines or tumor targets for weeks following the initial pre-activation. Conventional NK cell function is dependent upon a licensing signal, classically delivered by an inhibitory receptor engaging its cognate MHC class I ligand. How licensing status integrates with cytokine-induced memory-like NK cell responses is unknown...
November 25, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27893789/characterization-of-the-canine-mhc-class-i-dla-88-50101-peptide-binding-motif-as-a-prerequisite-for-canine-t-cell-immunotherapy
#14
Sharon M Barth, Christian M Schreitmüller, Franziska Proehl, Kathrin Oehl, Leonie M Lumpp, Daniel J Kowalewski, Moreno Di Marco, Theo Sturm, Linus Backert, Heiko Schuster, Stefan Stevanović, Hans-Georg Rammensee, Oliver Planz
There are limitations in pre-clinical settings using mice as a basis for clinical development in humans. In cancer, similarities exist between humans and dogs; thus, the dog patient can be a link in the transition from laboratory research on mouse models to clinical trials in humans. Knowledge of the peptides presented on MHC molecules is fundamental for the development of highly specific T cell-based immunotherapies. This information is available for human MHC molecules but is absent for the canine MHC. In the present study, we characterized the binding motif of dog leukocyte antigen (DLA) class I allele DLA-88*50101, using human C1R and K562 transfected cells expressing the DLA-88*50101 heavy chain...
2016: PloS One
https://www.readbyqxmd.com/read/27891225/unraveling-the-role-of-preexisting-immunity-in-prostate-cancer-patients-vaccinated-with-a-her-2-neu-hybrid-peptide
#15
Ioannis F Voutsas, Eleftheria A Anastasopoulou, Panagiotis Tzonis, Michael Papamichail, Sonia A Perez, Constantin N Baxevanis
BACKGROUND: Cancer vaccines aim at eliciting not only an immune response against specific tumor antigens, but also at enhancing a preexisting immunity against the tumor. In this context, we recently reported on the levels of preexisting immunity in prostate cancer patients vaccinated with the HER-2 hybrid peptide (AE37), during a phase I clinical trial. The purpose of the current study was to correlate between preexisting immunity to the native HER-2 peptide, AE36, and expression of HLA-A2 and -A24 molecules with the clinical outcome...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27890560/the-hippocampal-transcriptomic-signature-of-stress-resilience-in-mice-with-microglial-fractalkine-receptor-cx3cr1-deficiency
#16
Neta Rimmerman, Nofar Schottlender, Ronen Reshef, Nadav Dan-Goor, Raz Yirmiya
Clinical studies suggest that key genetic factors involved in stress resilience are related to the innate immune system. In the brain, this system includes microglia cells, which play a major role in stress responsiveness. Consistently, mice with deletion of the CX3CR1 gene (CX3CR1(-/-) mice), which in the brain is expressed exclusively by microglia, exhibit resilience to chronic stress. Here, we compared the emotional, cognitive, neurogenic and microglial responses to chronic unpredictable stress (CUS) between CX3CR1(-/-) and wild type (WT) mice...
November 23, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27889800/polymorphism-at-expressed-dq-and-dr-loci-in-five-common-equine-mhc-haplotypes
#17
Donald Miller, Rebecca L Tallmadge, Matthew Binns, Baoli Zhu, Yasmin Ali Mohamoud, Ayeda Ahmed, Samantha A Brooks, Douglas F Antczak
The polymorphism of major histocompatibility complex (MHC) class II DQ and DR genes in five common equine leukocyte antigen (ELA) haplotypes was determined through sequencing of mRNA transcripts isolated from lymphocytes of eight ELA homozygous horses. Ten expressed MHC class II genes were detected in horses of the ELA-A3 haplotype carried by the donor horses of the equine bacterial artificial chromosome (BAC) library and the reference genome sequence: four DR genes and six DQ genes. The other four ELA haplotypes contained at least eight expressed polymorphic MHC class II loci...
November 26, 2016: Immunogenetics
https://www.readbyqxmd.com/read/27880900/tailored-tumor-immunogenicity-reveals-regulation-of-cd4-and-cd8%C3%A2-t-cell-responses-against-cancer
#18
Sarah Knocke, Bettina Fleischmann-Mundt, Michael Saborowski, Michael P Manns, Florian Kühnel, Thomas C Wirth, Norman Woller
CD4 and CD8 T cells play a pivotal role in controlling tumor growth. However, the interplay of both cell types and their role in tumor suppression still remain elusive. In this study, we investigated the regulation of CD4 and CD8 T cell responses to different classes of tumor-specific antigens in liver cancer mouse models. Tumors were induced in p19Arf-deficient mice by hydrodynamic injection of transposon plasmids encoding NrasG12V and pre-defined tumor antigens. This allowed for assessing the regulation of tumor-specific CD4 and CD8 T cell responses...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880031/increased-levels-of-plasma-soluble-human-leukocyte-antigen-g-in-persistent-wheezy-infants
#19
Fulya Tahan, Hatice Eke Gungor, Himmet Haluk Akar, Berkay Saraymen
BACKGROUND: Human leukocyte antigen (HLA)-G is a non-classical major histocompatibility complex (MHC) class I antigen characterized by limited polymorphism in its coding region, unique tissue expression pattern in physiologic conditions and immunomodulatory properties. Recently, many studies suggest that the levels of sHLA-G were higher in atopic asthma and allergic rhinitis (AR). However, this remains to be uncertain in wheezy infants. In the present study, it was aimed to determine sHLA-G levels in wheezy infants...
November 23, 2016: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/27876605/role-of-zebrafish-nlrc5-in-antiviral-response-and-transcriptional-regulation-of-mhc-related-genes
#20
Xiao Man Wu, Yi Wei Hu, Na Na Xue, Shi Si Ren, Shan Nan Chen, Pin Nie, Ming Xian Chang
Intracellular NOD-like receptors (NLRs) are emerging as critical regulators of innate and adaptive immune responses. Although the NLR family member NLRC5 is functionally defined, the role of NLRC5 in regulating innate immune signaling has been controversial in mammals, and is poorly understood in teleost fish. In the present study, we report the functional characterization of zebrafish NLRC5. The cloned NLRC5 consists of 6435 bp which encodes 1746 amino acids. The N-terminal effector-binding domain of zebrafish NLRC5 is absent which is different from all other human NLRs...
November 20, 2016: Developmental and Comparative Immunology
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