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https://www.readbyqxmd.com/read/28534525/covalently-linked-dengue-virus-envelope-glycoprotein-dimers-reduce-exposure-of-the-immunodominant-fusion-loop-epitope
#1
Alexander Rouvinski, Wanwisa Dejnirattisai, Pablo Guardado-Calvo, Marie-Christine Vaney, Arvind Sharma, Stéphane Duquerroy, Piyada Supasa, Wiyada Wongwiwat, Ahmed Haouz, Giovanna Barba-Spaeth, Juthathip Mongkolsapaya, Félix A Rey, Gavin R Screaton
A problem in the search for an efficient vaccine against dengue virus is the immunodominance of the fusion loop epitope (FLE), a segment of the envelope protein E that is buried at the interface of the E dimers coating mature viral particles. Anti-FLE antibodies are broadly cross-reactive but poorly neutralizing, displaying a strong infection enhancing potential. FLE exposure takes place via dynamic 'breathing' of E dimers at the virion surface. In contrast, antibodies targeting the E dimer epitope (EDE), readily exposed at the E dimer interface over the region of the conserved fusion loop, are very potent and broadly neutralizing...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28534196/in-silico-analysis-of-shiga-toxins-stxs-to-identify-new-potential-vaccine-targets-for-shiga-toxin-producing-escherichia-coli
#2
Maryam Golshani, Mana Oloomi, Saeid Bouzari
Shiga toxins belong to a family of structurally and functionally related toxins serving as the main virulence factors for pathogenicity of the Shiga toxin-producing Escherichia coli (STEC) associating with Hemolytic uremic syndrome (HUS). At present, there is no effective treatment or prevention for HUS. The aim of the present study was to find conserved regions within the amino acid sequences of Stx1, Stx2 (Shiga toxin) and their variants. In this regard, In-silico identification of conformational continuous B cell and T-cell epitopes was performed in order to introduce new potential vaccine candidates...
December 2016: In Silico Pharmacology
https://www.readbyqxmd.com/read/28532654/flexible-ige-epitope-containing-domains-of-phl-p-5-cause-high-allergenic-activity
#3
Christoph Göbl, Margarete Focke-Tejkl, Nazanin Najafi, Evelyne Schrank, Tobias Madl, Simone Kosol, Christoph Madritsch, Yulia Dorofeeva, Sabine Flicker, Josef Thalhamer, Rudolf Valenta, Klaus Zangger, Nico Tjandra
This is the first study determining the three-dimensional structure of Phl p 5a which reveals a novel mechanism for high allergenic activity based on flexibly connected IgE-reactive domains which cross-link effector cell-bound IgE more efficiently than isolated rigid globular proteins. These findings may also form a basis for specific immunotherapy strategies.
May 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28532483/naturally-acquired-humoral-and-cellular-immune-responses-to-plasmodium-vivax-merozoite-surface-protein-8-in-patients-with-p-vivax-infection
#4
Yang Cheng, Bo Wang, Siriruk Changrob, Jin-Hee Han, Jetsumon Sattabongkot, Kwon-Soo Ha, Patchanee Chootong, Feng Lu, Jun Cao, Myat Htut Nyunt, Won Sun Park, Seok-Ho Hong, Chae Seung Lim, Takafumi Tsuboi, Eun-Taek Han
BACKGROUND: Thirty-one glycosylphosphatidylinositol (GPI)-anchored proteins of Plasmodium vivax, merozoite surface protein 1 (MSP1), MSP1 paralogue, MSP4, MSP5, MSP8, and MSP10 have been reported from homologs of Plasmodium falciparum by gene annotation with bioinformatics tools. These GPI-anchored proteins contain two epidermal growth factor (EGF)-like domains at its C-terminus. Here, P. vivax merozoite surface protein 8 (PvMSP8) are considered as potential targets of protective immunity...
May 22, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28532213/what-do-structures-tell-us-about-chemokine-receptor-function-and-antagonism
#5
Irina Kufareva, Martin Gustavsson, Yi Zheng, Bryan S Stephens, Tracy M Handel
Chemokines and their cell surface G protein-coupled receptors are critical for cell migration, not only in many fundamental biological processes but also in inflammatory diseases and cancer. Recent X-ray structures of two chemokines complexed with full-length receptors provided unprecedented insight into the atomic details of chemokine recognition and receptor activation, and computational modeling informed by new experiments leverages these insights to gain understanding of many more receptor:chemokine pairs...
May 22, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28531814/targeting-egfr-her2-heterodimerization-with-a-novel-anti-her2-domain-ii-iii-antibody
#6
Xiaojie Yu, Lingfei Wang, Yafeng Shen, Chao Wang, Yajun Zhang, Yanchun Meng, Yang Yang, Beibei Liang, Bo Zhou, Huajing Wang, Huafeng Wei, Changhai Lei, Shi Hu, Bohua Li
HER2, a ligand-free tyrosine kinase receptor of the HER family, is frequently overexpressed in breast cancer. The anti-HER2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer. Despite the effectiveness of trastuzumab, its efficacy remains variable and often modest. Thus, there is an urgent need to improve ErbB2-targeting therapy. Here, we describe a novel anti-HER2 antibody, 7C3, which was developed using hybridoma technique. Structural analysis confirms that the epitope of this antibody is in domain II/III of HER2...
May 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28530508/influence-of-transmitted-virus-on-the-host-s-immune-response-a-case-study
#7
Shahzma Merani, Michaela Lucas, Pooja Deshpande, Katja Pfafferott, Abha Chopra, Don Cooper, Shay Leary, Fabio Luciani, Silvana Gaudieri
Host hepatitis C virus (HCV)-specific T cell responses and the ability of the virus to escape this response are important correlates of infection outcome. Understanding this host-viral interplay has been difficult given the often asymptomatic nature of acute HCV infection. We studied a recent transmission case to determine whether adapted viral strains can be transmitted and influence the recipient's anti-HCV T cell response. The diversity of viral populations was examined using next-generation sequencing, and HCV-specific T cell interferon (IFN)-γ responses were assessed using a peptide panel representing the autologous viruses...
May 22, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28530170/k-modulates-genetic-competence-and-the-stress-regulon-of-streptococcus-mutans
#8
Gursonika Binepal, Iwona B Wenderska, Paula Crowley, Richard N Besingi, Dilani B Senadheera, L Jeannine Brady, Dennis G Cvitkovitch
Potassium (K+) is the most abundant cation in dental plaque fluid. Previously, we reported the link between K+ transport via Trk2 in Streptococcus mutans and its two critical virulence attributes: acid tolerance and surface adhesion. Herein, we build further on the intimate link between K+ levels and S. mutans biology. High (>25 mM) versus low (≤5 mM) K+ concentrations in the growth medium affected conformational epitopes of cell surface-localized adhesin P1. At low K+, the expression of stress response elements gcrR and codY, cell-adhesion-associated genes such as spaP and metabolism-associated genes such as bglP was induced at stationary phase (P<0...
May 22, 2017: Microbiology
https://www.readbyqxmd.com/read/28529511/characterization-of-cd4-t-cell-epitopes-of-infliximab-and-rituximab-identified-from-healthy-donors
#9
Moustafa Hamze, Sylvain Meunier, Anette Karle, Abdelaziz Gdoura, Amélie Goudet, Natacha Szely, Marc Pallardy, Franck Carbonnel, Sebastian Spindeldreher, Xavier Mariette, Corinne Miceli-Richard, Bernard Maillère
The chimeric antibodies anti-CD20 rituximab (Rtx) and anti-TNFα infliximab (Ifx) induce antidrug antibodies (ADAs) in many patients with inflammatory diseases. Because of the key role of CD4 T lymphocytes in the initiation of antibody responses, we localized the CD4 T cell epitopes of Rtx and Ifx. With the perspective to anticipate immunogenicity of therapeutic antibodies, identification of the CD4 T cell epitopes was performed using cells collected in healthy donors. Nine T cell epitopes were identified in the variable chains of both antibodies by deriving CD4 T cell lines raised against either Rtx or Ifx...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28528961/gp5-of-porcine-reproductive-and-respiratory-syndrome-virus-prrsv-as-a-target-for-homologous-and-broadly-neutralizing-antibodies
#10
REVIEW
Luca N Popescu, Benjamin R Trible, Nanhua Chen, Raymond R R Rowland
Virus neutralization (VN) responses range from narrowly focused antibodies with only homologous neutralizing activity against the virus used for infection, to antibodies that can neutralize both Type 1 and Type 2 viruses, referred to as broadly neutralizing antibody (bnAb). Even though neutralizing epitopes are likely distributed among several structural glycoproteins, this paper focuses on the ectodomain region of GP5 as a model system for investigating the role for neutralizing and non-neutralizing antibodies in protection and disease...
April 29, 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28527237/the-n-terminus-of-the-prion-protein-is-a-toxic-effector-regulated-by-the-c-terminus
#11
Bei Wu, Alex J McDonald, Kathleen Markham, Celeste B Rich, Kyle P Mchugh, Jörg Tatzelt, David W Colby, Glenn L Millhauser, David A Harris
PrP(C), the cellular isoform of the prion protein, serves to transduce the neurotoxic effects of PrP(Sc), the infectious isoform, but how this occurs is mysterious. Here, using a combination of electrophysiological, cellular, and biophysical techniques, we show that the flexible, N-terminal domain of PrP(C) functions as a powerful toxicity-transducing effector whose activity is tightly regulated in cis by the globular C-terminal domain. Ligands binding to the N-terminal domain abolish the spontaneous ionic currents associated with neurotoxic mutants of PrP, and the isolated N-terminal domain induces currents when expressed in the absence of the C-terminal domain...
May 20, 2017: ELife
https://www.readbyqxmd.com/read/28526816/delineation-of-b-cell-epitopes-of-salmonella-enterica-serovar-typhi-hemolysin-e-potential-antibody-therapeutic-target
#12
Chai Fung Chin, Jing Yi Lai, Yee Siew Choong, Amy Amilda Anthony, Asma Ismail, Theam Soon Lim
Hemolysin E (HlyE) is an immunogenic novel pore-forming toxin involved in the pathogenesis of typhoid fever. Thus, mapping of B-cell epitopes of Salmonella enterica serovar Typhi (S. Typhi) is critical to identify key immunogenic regions of HlyE. A random 20-mer peptide library was used for biopanning with enriched anti-HlyE polyclonal antibodies from typhoid patient sera. Bioinformatic tools were used to refine, analyze and map the enriched peptide sequences against the protein to identify the epitopes. The analysis identified both linear and conformational epitopes on the HlyE protein...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526759/il-2-high-tissue-resident-t-cells-in-the-human-liver-sentinels-for-hepatotropic-infection
#13
Laura J Pallett, Jessica Davies, Emily J Colbeck, Francis Robertson, Navjyot Hansi, Nicholas J W Easom, Alice R Burton, Kerstin A Stegmann, Anna Schurich, Leo Swadling, Upkar S Gill, Victoria Male, TuVinh Luong, Amir Gander, Brian R Davidson, Patrick T F Kennedy, Mala K Maini
The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet(lo)Eomes(lo)Blimp-1(hi)Hobit(lo) T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69(+)CD103(+) CXCR6(+)CXCR3(+))...
May 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28526580/biomarkers-for-rheumatoid-arthritis-from-molecular-processes-to-diagnostic-applications-current-concepts-and-future-perspectives
#14
REVIEW
Britt Nakken, Gábor Papp, Vidar Bosnes, Margit Zeher, György Nagy, Peter Szodoray
Early diagnosis and immediately started appropriate treatment are mandatory for the prevention of radiographic progression, functional disability and unfavourable disease outcome in rheumatoid arthritis (RA). The current classification criteria for RA include two different types of biomarkers representing inflammatory processes, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) or immune processes including autoantibodies, such as rheumatoid factor (RF) and antibodies against citrullinated proteins (ACPA)...
May 16, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28525755/antibodies-from-a-human-survivor-define-sites-of-vulnerability-for-broad-protection-against-ebolaviruses
#15
Anna Z Wec, Andrew S Herbert, Charles D Murin, Elisabeth K Nyakatura, Dafna M Abelson, J Maximilian Fels, Shihua He, Rebekah M James, Marc-Antoine de La Vega, Wenjun Zhu, Russell R Bakken, Eileen Goodwin, Hannah L Turner, Rohit K Jangra, Larry Zeitlin, Xiangguo Qiu, Jonathan R Lai, Laura M Walker, Andrew B Ward, John M Dye, Kartik Chandran, Zachary A Bornholdt
Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525748/ebolavirus-s-foibles
#16
Seiya Yamayoshi, Yoshihiro Kawaoka
Ebola virus disease poses a global health threat. Here, two studies by Wec et al. and Zhao et al. identified vulnerability in an internal fusion loop of an ebolavirus glycoprotein. Monoclonal antibodies elicited from immunization and isolated from a human survivor that recognized epitopes in this area neutralized all five ebolaviruses, guiding the development of a pan-ebolavirus immunotherapy.
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525653/predicted-philogeny-secondary-conformational-structure-and-epitope-antigenicity-of-immunological-sequences-in-poultry
#17
L J Lara, A P Peconick, É J Fassani, A M P Júnior, P R B Chalfun, D L Raymundo, T A Barçante, J M de P Barçante
Poultry production is faced with different types of stresses that are responsible for issues of animal welfare as well as for economic losses. Moreover, the immunity decreases when animals are stressed. In silico analyses are important in reducing the cost and in increasing the accuracy of scientific results. A bioinformatics tool was used to perform ontology studies on 15 different immunological sequences of poultry. The mRNA structures and sequences with maximum antigenic residues were also predicted. No homology was found between the sequences of poultry and mammals...
May 18, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28525314/malaria-parasite-limp-protein-regulates-sporozoite-gliding-motility-and-infectivity-in-mosquito-and-mammalian-hosts
#18
Jorge M Santos, Saskia Egarter, Vanessa Zuzarte-Luís, Hirdesh Kumar, Catherine A Moreau, Jessica Kehrer, Andreia Pinto, Mário da Costa, Blandine Franke-Fayard, Chris J Janse, Friedrich Frischknecht, Gunnar R Mair
Gliding motility allows malaria parasites to migrate and invade tissues and cells in different hosts. It requires parasite surface proteins to provide attachment to host cells and extracellular matrices. Here, we identify the Plasmodium protein LIMP (the name refers to a gliding phenotype in the sporozoite arising from epitope tagging of the endogenous protein) as a key regulator for adhesion during gliding motility in the rodent malaria model P. berghei. Transcribed in gametocytes, LIMP is translated in the ookinete from maternal mRNA, and later in the sporozoite...
May 2, 2017: ELife
https://www.readbyqxmd.com/read/28525280/self-healing-self-assembled-%C3%AE-sheet-peptide-poly-%C3%AE-glutamic-acid-hybrid-hydrogels
#19
David E Clarke, E Thomas Pashuck, Sergio Bertazzo, Jonathan V M Weaver, Molly M Stevens
Self-assembled biomaterials are an important class of materials that can be injected and formed in situ. However, they often are not able to meet the mechanical properties necessary for many biological applications, losing mechanical properties at low strains. We synthesized hybrid hydrogels consisting of a poly(γ-glutamic acid) polymer network physically cross-linked via grafted self-assembling β-sheet peptides to provide non-covalent cross-linking through β-sheet assembly, reinforced with a polymer backbone to improve strain stability...
May 19, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28522882/monoclonal-suncus-antibodies-generation-of-fusion-partners-to-produce-suncus-suncus-hybridomas
#20
Yoshikazu Sado, Satoko Inoue, Yasuko Tomono, Makoto Matsuyama, Masaki Fukushima, Toshitaka Oohashi, Takamichi Jogahara, Sen-Ichi Oda
We used suncus (Suncus murinus; house musk shrew) to generate partner cells for cell fusion to produce suncus monoclonal antibodies. Suncus are insectivores that are genetically distant to rodents, and recognize antigens and epitopes that are not immunogenic in mice and rats, which are the animals most commonly used in basic life science research and from which monoclonal antibodies are usually produced. To date, monoclonal antibodies from suncus have not been generated due to the lack of a plasmacytoma fusion partner...
April 27, 2017: Acta Histochemica et Cytochemica
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