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https://www.readbyqxmd.com/read/28446902/modulation-of-macrophage-responses-by-cmx-a-fusion-protein-composed-of-ag85c-mpt51-and-hspx-from-mycobacterium-tuberculosis
#1
Adeliane C da Costa, Danilo P de Resende, Bruno de P O Santos, Karina F Zoccal, Lúcia H Faccioli, André Kipnis, Ana P Junqueira-Kipnis
Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is a vaccine used to prevent tuberculosis (TB). Due to the poor protection conferred by BCG in adults, new, more effective formulations have been developed. A recombinant BCG vaccine expressing the CMX fusion protein Ag85c_MPT51_HspX (rBCG-CMX) induced Th1 and Th17 responses and provided better protection than BCG. It has been shown that Mycobacterium smegmatis expressing CMX also induces better protection than BCG and is a strong macrophage activator. The aim of the present study was to evaluate macrophage activation by the recombinant CMX fusion protein and by rBCG-CMX and to evaluate their ability to generate vaccine-specific immune responses...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28446731/the-antigenic-identity-of-human-class-i-mhc-phosphopeptides-is-critically-dependent-upon-phosphorylation-status
#2
Fiyaz Mohammed, Daniel H Stones, Angela L Zarling, Carrie R Willcox, Jeffrey Shabanowitz, Kara L Cummings, Donald F Hunt, Mark Cobbold, Victor H Engelhard, Benjamin E Willcox
Dysregulated post-translational modification provides a source of altered self-antigens that can stimulate immune responses in autoimmunity, inflammation, and cancer. In recent years, phosphorylated peptides have emerged as a group of tumour-associated antigens presented by MHC molecules and recognised by T cells, and represent promising candidates for cancer immunotherapy. However, the impact of phosphorylation on the antigenic identity of phosphopeptide epitopes is unclear. Here we examined this by determining structures of MHC-bound phosphopeptides bearing canonical position 4-phosphorylations in the presence and absence of their phosphate moiety, and examining phosphopeptide recognition by the T cell receptor (TCR)...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445787/adipose-derived-stem-cells-were-impaired-in-restricting-cd4-t-cell-proliferation-and-polarization-in-type-2-diabetic-apoe-mouse
#3
Ming-Hao Liu, Ya Li, Lu Han, Yao-Yuan Zhang, Di Wang, Zhi-Hao Wang, Hui-Min Zhou, Ming Song, Yi-Hui Li, Meng-Xiong Tang, Wei Zhang, Ming Zhong
BACKGROUND: Atherosclerosis (AS) is the most common and serious complication of type 2 diabetes mellitus (T2DM) and is accelerated via chronic systemic inflammation rather than hyperglycemia. Adipose tissue is the major source of systemic inflammation in abnormal metabolic state. Pro-inflammatory CD4(+)T cells play pivotal role in promoting adipose inflammation. Adipose-derived stem cells (ADSCs) for fat regeneration have potent ability of immunosuppression and restricting CD4(+)T cells as well...
April 23, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28441398/the-effects-of-immune-protein-cd3%C3%AE-development-and-degeneration-of-retinal-neurons-after-optic-nerve-injury
#4
Tao He, Xavier Mortensen, Ping Wang, Ning Tian
Major histocompatibility complex (MHC) class I molecules and their receptors play fundamental roles in neuronal death during diseases. T-cell receptors (TCR) function as MHCI receptor on T-cells and both MHCI and a key component of TCR, CD3ζ, are expressed by mouse retinal ganglion cells (RGCs) and displaced amacrine cells. Mutation of these molecules compromises the development of RGCs. We investigated whether CD3ζ regulates the development and degeneration of amacrine cells after RGC death. Surprisingly, mutation of CD3ζ not only impairs the proper development of amacrine cells expressing CD3ζ but also those not expressing CD3ζ...
2017: PloS One
https://www.readbyqxmd.com/read/28440548/contact-sensitizers-trigger-human-cd1-autoreactive-t-cell-responses
#5
Richard J Betts, Adrijana Perkovic, Subhashree Mahapatra, Aurélia Del Bufalo, Kaddy Camara, Amy R Howell, Silvia Martinozzi Teissier, Gennaro De Libero, Lucia Mori
Allergic contact dermatitis is a primarily T-cell-mediated inflammatory skin disease induced by exposure to small molecular-weight haptens, which covalently bind to proteins. The abundance of cutaneous T cells that recognize CD1a antigen-presenting molecules raises the possibility that MHC-independent antigen presentation may be relevant in some hapten-driven immune responses. Here we examine the ability of contact sensitizers to influence CD1-restricted immunity. Exposure of human antigen-presenting cells such as monocyte-derived dendritic cells and THP-1 cells to the prototypical contact sensitizer dinitrochlorobenzene potentiated the response of CD1a- and CD1d-autoreactive T cells, which released a vast array of cytokines in a CD1- and TCR-dependent manner...
April 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28438433/contribution-of-inhibitory-receptor-tigit-to-nk-cell-education
#6
Yuke He, Hui Peng, Rui Sun, Haiming Wei, Hans-Gustaf Ljunggren, Wayne M Yokoyama, Zhigang Tian
Engagement of inhibitory receptors by cognate host MHC-I molecules triggers NK cell education, resulting in functional maturation and allowing NK cells to sense missing-self. However, NK cells also express inhibitory receptors for non-MHC-I ligands and their role in NK cell education is poorly understood. TIGIT is a recently identified inhibitory receptor that recognizes a non-MHC-I ligand CD155. Here, we demonstrated that TIGIT(+) NK cells from wild-type mice exerted augmented responsiveness to various stimuli, including targets that lacked expression of CD155 ligand...
April 21, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28433952/what-chickens-might-tell-us-about-the-mhc-class-ii-system
#7
REVIEW
Aimée Parker, Jim Kaufman
Almost all knowledge about the structure and function of MHC class II molecules outside of mammals comes from work with chickens. Most of the genes implicated in the class II system are present in chickens, so it is likely that the machinery of antigen processing and peptide-loading is similar to mammals. However, there is only one isotype (lineage) of classical class II genes, with one monomorphic DR-like BLA gene and two polymorphic BLB genes, located near one DMA and two DMB genes. The DMB2 and BLB2 genes are widely expressed at high levels, whereas the DMB1 and BLB1 genes are only expressed at highest levels in spleen and intestine, suggesting the possibility of two class II systems in chickens...
April 20, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28433527/characterization-of-leukocyte-subsets-in-buffalo-bubalus-bubalis-with-cross-reactive-monoclonal-antibodies-specific-for-bovine-mhc-class-i-and-class-ii-molecules-and-leukocyte-differentiation-molecules
#8
Francesco Grandoni, Mahmoud M Elnaggar, Gaber S Abdellrazeq, Federica Signorelli, Lindsay M Fry, Cinzia Marchitelli, Victoria Hulubei, Samy A Khaliel, Helmy A Torky, William C Davis
Although buffaloes (Bubalus bubalis) are a major component of the livestock industry worldwide, limited progress has been made in the study of the mechanisms regulating the immune response to pathogens and parasites affecting their health and productivity. This has been, in part, attributable to the limited availability of reagents to study immune responses in buffalo. As reported here, a set of cross-reactive monoclonal antibodies (mAbs), developed against bovine, ovine and caprine leukocyte differentiation molecules (LDM) and major histocompatibility complex (MHC) molecules, were identified and used to compare expression of LDM in Italian and Egyptian buffalo...
April 20, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28432936/the-immunosuppressive-characteristics-of-fb1-by-inhibition-of-maturation-and-function-of-bmdcs
#9
Yinhuan Li, Yanhong Fan, Bingbing Xia, Qiuping Xiao, Qingqing Wang, Weidong Sun, Haibin Zhang, Chenghua He
Fumonisin B1 (FB1) is one kind of mycotoxins that has the neurotoxicity, carcinogenicity, hepatotoxicity and immunotoxicity produced by the fungus Fusarium verticillioides, which commonly infects corn and other crops and is harmful to animal and human health upon consumption of FB1-contaminated feed or food. However, the mechanism of immunotoxicity, especially the immunosuppression induced by FB1 is still unclear. The most pivotal cells in the induction of immune responses are dendritic cells (DCs). In this study, we used murine bone marrow-derived dendritic cells (BMDCs) as a model system to elucidate the effect of FB1 on the function of BMDCs through biological methods...
April 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28428785/interferon-gamma-induces-changes-in-natural-killer-nk-cell-ligand-expression-and-alters-nk-cell-mediated-lysis-of-pediatric-cancer-cell-lines
#10
Arianexys Aquino-López, Vladimir V Senyukov, Zlatko Vlasic, Eugenie S Kleinerman, Dean A Lee
Natural killer (NK) cells have therapeutic potential for cancer due to their capacity for targeting tumor cells without prior sensitization. Our laboratory has developed an NK cell expansion protocol that generates large quantities of NK cells for therapeutic infusion that secret 20 times the amount of interferon gamma (IFNγ) than resting NK cells. IFNγ can upregulate major histocompatibility complex (MHC)-class I, an inhibitory ligand for NK cells, but can also upregulate intercellular adhesion molecule 1 (ICAM-1) which promotes NK:target cell interaction for an efficient lysis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28425917/tapbpr-bridges-udp-glucose-glycoprotein-glucosyltransferase-1-onto-mhc-class-i-to-provide-quality-control-in-the-antigen-presentation-pathway
#11
Andreas Neerincx, Clemens Hermann, Robin Antrobus, Andy van Hateren, Huan Cao, Nico Trautwein, Stefan Stevanović, Tim Elliott, Janet E Deane, Louise H Boyle
Recently we revealed that TAPBPR is a peptide exchange catalyst important for optimal peptide selection by MHC class I molecules. Here we asked if any other co-factors associate with TAPBPR which would explain its effect on peptide selection. We identify an interaction between TAPBPR and UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), a folding sensor in the calnexin/calreticulin quality control cycle known to regenerate the Glc1Man9GlcNAc2 moiety on glycoproteins. Our results suggest the formation of a multimeric complex, dependent on a conserved cysteine at position 94 in TAPBPR, in which TAPBPR promotes the association of UGT1 with peptide-receptive class I molecules...
April 20, 2017: ELife
https://www.readbyqxmd.com/read/28419545/intermolecular-interactions-between-dm%C3%AE-and-dm%C3%AE-proteins-in-bula-dm-complex-of-water-buffalo-bubalus-bubalis
#12
Leena Rawal, Deepak Panwar, Sher Ali
The major histocompatibility complex (MHC) with its 3 classes represents a cluster of tightly linked genes with defined immunological and non-immunological functions. The DM, a MHC class II molecule is formed by the non-covalent association of DMα and DMβ chains. It binds with the processed peptide antigens and presents them to T lymphocytes, thereby triggering the immune responses. Startlingly, the expression pattern and structural organization of DMα and DMβ proteins in buffalo remains undefined. We isolated and purified the DMα and DMβ proteins from Bubalus bubalis using gel filtration chromatography...
April 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28419492/expression-and-trafficking-of-mhc-related-protein-1-mr1
#13
REVIEW
R Lamichhane, J E Ussher
MHC related protein 1 (MR1) is a non-polymorphic MHC class IB antigen presenting molecule that is the restricting molecule for mucosal associated invariant T (MAIT) cells, a prominent population of innate-like antibacterial T cells. The MAIT cell-MR1 axis represents a new paradigm in antigen presentation, with the MR1 ligand derived from vitamin B compounds or their metabolic precursors. Many bacteria and some fungi produce the activating ligand for MR1. In evolution, MR1 is highly conserved in most, but not all, mammals...
April 17, 2017: Immunology
https://www.readbyqxmd.com/read/28410529/ifn%C3%AE-enhances-cytotoxic-efficiency-of-the-cytotoxic-t-lymphocytes-against-human-glioma-cells
#14
Shengwen Shao, Eric Risch, Danielle Burner, Lingeng Lu, Boris Minev, Wenxue Ma
Cytotoxic T lymphocytes (CTLs) are a key player in cancer immunotherapies, and MHC class I molecules on the cell surface are crucial for cellular recognition. However, the aberrant expression of MHC class I molecules is frequently found in various malignancies. IFNγ has dual functions in cancer progression, and its effect on tumor immunity is controversial. To investigate whether IFNγ can enhance cytotoxic efficiency of the tumor antigen-specific CTLs, we generated the CTLs using modified human dendritic cells as antigen presenting cells, then studied the activities of CTLs on human leukocyte antigen (HLA)-A2 positive glioma cells treated with, or without IFNγ...
April 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28408181/peptide-conjugated-nanoparticles-reduce-positive-co-stimulatory-expression-and-t-cell-activity-to-induce-tolerance
#15
Robert Kuo, Eiji Saito, Stephen D Miller, Lonnie D Shea
Targeted approaches to treat autoimmune diseases would improve upon current therapies that broadly suppress the immune system and lead to detrimental side effects. Antigen-specific tolerance was induced using poly(lactide-co-glycolide) nanoparticles conjugated with disease-relevant antigen to treat a model of multiple sclerosis. Increasing the nanoparticle dose and amount of conjugated antigen both resulted in more durable immune tolerance. To identify active tolerance mechanisms, we investigated downstream cellular and molecular events following nanoparticle internalization by antigen-presenting cells...
April 10, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28402951/characterization-of-a-secreted-macrophage-migration-inhibitory-factor-homologue-of-the-parasitic-nematode-haemonchus-contortus-acting-at-the-parasite-host-cell-interface
#16
Yujian Wang, MingMin Lu, Shuai Wang, Muhammad Ehsan, RuoFeng Yan, XiaoKai Song, LiXin Xu, XiangRui Li
Modulation and suppression of the immune response of the host by nematode parasites have been reported extensively and the migration inhibitory factor (MIF) is identified as one of the major immunomodulator. In the present study, we cloned and produced recombinant MIF protein from the small ruminant's nematode parasite Haemonchus contortus (rHCMIF-1), and investigated its immunomodulatory effects on goat monocyte. Enzymatic assays indicated that rHCMIF-1 possessed tautomerase activity. Immunohistochemical test demonstrated that the native HCMIF-1 protein was predominantly localized at the body surface and internal surface of the worm's gut...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401156/computational-identification-and-characterization-of-a-promiscuous-t-cell-epitope-on-the-extracellular-protein-85b-of-mycobacterium-spp-for-peptide-based-subunit-vaccine-design
#17
Md Saddam Hossain, Abul Kalam Azad, Parveen Afroz Chowdhury, Mamoru Wakayama
Tuberculosis (TB) is a reemerging disease that remains as a leading cause of morbidity and mortality in humans. To identify and characterize a T-cell epitope suitable for vaccine design, we have utilized the Vaxign server to assess all antigenic proteins of Mycobacterium spp. recorded to date in the Protegen database. We found that the extracellular protein 85B displayed the most robust antigenicity among the proteins identified. Computational tools for identifying T-cell epitopes predicted an epitope, 181-QQFIYAGSLSALLDP-195, that could bind to at least 13 major histocompatibility complexes, revealing the promiscuous nature of the epitope...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28399128/creation-of-an-immunodeficient-hla-transgenic-mouse-humamice-and-functional-validation-of-human-immunity-after-transfer-of-hla-matched-human-cells
#18
Yang Zeng, Bingrun Liu, Marie-Thérèse Rubio, Xinyue Wang, David M Ojcius, Ruoping Tang, Antoine Durrbach, Zhitao Ru, Yusen Zhou, Yu-Chun Lone
Research on human immunology has been hindered by the lack of optimal small animal models, given that the protective immune responses of human and non-human species show significant differences. However, due to ethical constraints[1] and the high cost of clinical trials, it is urgent to improve the current animal models that can mimic faithfully human physiology, particularly the human immune system (HIS). HIS mice had been generated recently by engrafting human hematopoietic stem cells (hHSCs) or human peripheral mononuclear cells (hPBMCs) into highly immuno-deficient mice such as NSG, NOG or NRG mice...
2017: PloS One
https://www.readbyqxmd.com/read/28396666/dynamic-changes-in-the-intracellular-association-of-selected-rab-small-gtpases-with-mhc-class-ii-and-dm-during-dendritic-cell-maturation
#19
Gibrán Pérez-Montesinos, Orestes López-Ortega, Jessica Piedra-Reyes, Laura C Bonifaz, José Moreno
Antigen processing for presentation by major histocompatibility complex class II (MHCII) molecules requires the latter to travel through the endocytic pathway together with its chaperons: the invariant chain (Ii) and DM. Nevertheless, the nature of the compartments where MHCII molecules travel to acquire peptides lacks definition regarding molecules involved in intracellular vesicular trafficking, such as Rab small GTPases. We aimed to define which Rab proteins are present during the intracellular transport of MHCII, DM, and Ii through the endocytic pathway on their route to the cell surface during dendritic cell (DC) maturation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28396662/the-role-of-dendritic-cell-maturation-in-the-induction-of-insulin-dependent-diabetes-mellitus
#20
REVIEW
Jacques C Mbongue, Hector A Nieves, Timothy W Torrez, William H R Langridge
Dendritic cells (DCs) are the dominant class of antigen-presenting cells in humans and are largely responsible for the initiation and guidance of innate and adaptive immune responses involved in maintenance of immunological homeostasis. Immature dendritic cells (iDCs) phagocytize pathogens and toxic proteins and in endosomal vesicles degrade them into small fragments for presentation on major histocompatibility complex (MHC) II receptor molecules to naïve cognate T cells (Th0). In addition to their role in stimulation of immunity, DCs are involved in the induction and maintenance of immune tolerance toward self-antigens...
2017: Frontiers in Immunology
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