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https://www.readbyqxmd.com/read/29775667/identification-of-novel-hla-a11-restricted-t-cell-epitopes-in-the-ebola-virus-nucleoprotein
#1
Dan Li, Pei Li, Nianping Song, Yuting Jiang, Yang Zeng, Guangyu Zhao, Yunzhi Fa, Huahu Ye, Yuchun Lone, Yusen Zhou, Shihui Sun, Lin Zeng
The Ebola virus (EBOV) is a very contagious virus that is highly fatal in humans and animals. The largest epidemic was in West Africa in 2014, in which over 11,000 people died. However, to date, there are no licensed vaccines against it. Studies show that CD4+ and CD8+ T-cell responses, especially cytotoxic T-lymphocyte (CTL) responses, play key roles in protecting individuals from EBOV infection. Since HLA-restricted epitope vaccines are likely to be effective and safe immunization strategies for infectious diseases, the present study screened for CTL epitopes in the EBOV-nucleoprotein that are restricted by HLA-A11 (a common allele in Chinese people)...
May 15, 2018: Microbes and Infection
https://www.readbyqxmd.com/read/29775653/atomic-structure-of-a-rationally-engineered-gene-delivery-vector-aav2-5
#2
Matthew Burg, Claire Rosebrough, Lauren M Drouin, Antonette Bennett, Mario Mietzsch, Paul Chipman, Robert McKenna, Duncan Sousa, Mark Potter, Barry Byrne, R Jude Samulski, Mavis Agbandje-McKenna
AAV2.5 represents the first structure-guided in-silico designed Adeno-associated virus (AAV) gene delivery vector. This engineered vector combined the receptor attachment properties of AAV serotype 2 (AAV2) with the muscle tropic properties of AAV1, and exhibited an antibody escape phenotype because of a modified antigenic epitope. To confirm the design, the structure of the vector was determined to a resolution of 2.78 Å using cryo-electron microscopy and image reconstruction. The structure of the major viral protein (VP), VP3, was ordered from residue 219 to 736, as reported for other AAV structures, and the five AAV2...
May 15, 2018: Journal of Structural Biology
https://www.readbyqxmd.com/read/29775620/a-monoclonal-antibody-sandwich-elisa-for-vitamin-d-binding-protein-vdbp-is-unaffected-by-gc-globulin-phenotype-peptides-and-actin-and-demonstrates-reduced-levels-in-sepsis-and-non-sepsis-intensive-care-patients
#3
Katrina Hong, Christopher M Florkowski, Matthew P Doogue, Peter A Elder, John G Lewis
The measurement of vitamin D-binding protein (VDBP) by immunoassay has been confounded by variable antibody recognition of the Gc1s, Gc1F and Gc2 phenotypes. This has led to spurious conclusions regarding vitamin D status in different ethnic groups. In order to overcome these problems there is a requirement for VDBP antibodies that are unaffected by phenotype status. Here we report the generation and testing of three monoclonal antibodies to VDBP which recognise linear epitopes and are unaffected by vast molar excesses of synthetic peptides spanning these phenotypic domains...
May 15, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29774846/occupation-associated-fatal-limbic-encephalitis-caused-by-variegated-squirrel-bornavirus-1-germany-2013
#4
Dennis Tappe, Kore Schlottau, Daniel Cadar, Bernd Hoffmann, Lorenz Balke, Burkhard Bewig, Donata Hoffmann, Philip Eisermann, Helmut Fickenscher, Andi Krumbholz, Helmut Laufs, Monika Huhndorf, Maria Rosenthal, Walter Schulz-Schaeffer, Gabriele Ismer, Sven-Kevin Hotop, Mark Brönstrup, Anthonina Ott, Jonas Schmidt-Chanasit, Martin Beer
Limbic encephalitis is commonly regarded as an autoimmune-mediated disease. However, after the recent detection of zoonotic variegated squirrel bornavirus 1 in a Prevost's squirrel (Callosciurus prevostii) in a zoo in northern Germany, we retrospectively investigated a fatal case in an autoantibody-seronegative animal caretaker who had worked at that zoo. The virus had been discovered in 2015 as the cause of a cluster of cases of fatal encephalitis among breeders of variegated squirrels (Sciurus variegatoides) in eastern Germany...
June 2018: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29774024/quantification-of-hla-dm-dependent-major-histocompatibility-complex-of-class-ii-immunopeptidomes-by-the-peptide-landscape-antigenic-epitope-alignment-utility
#5
Miguel Álvaro-Benito, Eliot Morrison, Esam T Abualrous, Benno Kuropka, Christian Freund
The major histocompatibility complex of class II (MHCII) immunopeptidome represents the repertoire of antigenic peptides with the potential to activate CD4+ T cells. An understanding of how the relative abundance of specific antigenic epitopes affects the outcome of T cell responses is an important aspect of adaptive immunity and offers a venue to more rationally tailor T cell activation in the context of disease. Recent advances in mass spectrometric instrumentation, computational power, labeling strategies, and software analysis have enabled an increasing number of stratified studies on HLA ligandomes, in the context of both basic and translational research...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29773713/a-thumbwheel-mechanism-for-apoa1-activation-of-lcat-activity-in-hdl
#6
Allison L Cooke, Jamie Morris, John T Melchior, Scott E Street, W Gray Jerome, Rong Huang, Andrew B Herr, Loren E Smith, Jere P Segrest, Alan T Remaley, Amy S Shah, Thomas B Thompson, W Sean Davidson
APOA1 is the most abundant protein in HDL. It modulates interactions that affect HDLs cardioprotective functions, in part via its activation of the enzyme LCAT. On nascent, discoidal HDL, APOA1 comprises 10 alpha-helical repeats arranged in an anti-parallel, stacked-ring structure that encapsulates a lipid bilayer. Previous chemical cross-linking studies suggested that these APOA1 rings can adopt at least two different orientations, or registries, with respect to each other; however, the functional impact of these structural changes is unknown...
May 17, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29773099/-toxoplasma-gondii-rop38-promotes-the-maturation-of-dendritic-cells-mediated-by-tlr4
#7
Heng Zhang, Shanghua Wu, Zhiqiang Shi, Shan Wang, Wei Lu, Yizhen Wu, Pei Sun, Qianming Xu
Objective To investigate the effect of rhoptry protein 38 (ROP38) from Toxoplasma gondii (T. gondii) on the maturation of dendritic cells (DCs) by Toll-like receptor 4 (TLR4) induction in vitro. Methods The total RNA from T. gondii RH strain was extracted by guanidine thiocyanate method, and then cDNA was synthesized with reverse transcription reaction. After ROP38 gene was amplified by PCR, the recombinant pGEX-4T-ROP38 was constructed and expressed under IPTG induction. The recombinant ROP38 protein was detected by SDS-PAGE and Western blot analysis...
March 2018: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29772544/antigen-specific-therapy-of-graves%C3%A2-disease-and-orbitopathy-by-induction-of-tolerance
#8
Martin Ungerer, Julia Fabbender, Hans-Peter Holthoff
Graves´ disease is an autoimmune disorder, which is characterized by stimulatory antibodies targeting the human thyrotropin receptor (TSHR), resulting in hyperthyroidism and multiple organ damage. The disease can be modelled in mice using adenoviral immunizations with the extracellular A subunit of the TSHR, which induces a long-term stable disease state. TSHR binding cAMP-stimulatory antibodies, thyroid enlargement, elevated serum thyroxin levels, tachycardia, cardiac hypertrophy and orbitopathy are observed in these Ad-TSHR-immunized mice...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772075/cd6-mabs-differ-in-epitope-kinetics-and-mechanism-of-action
#9
Lee I Garner, Andrew Hartland, Johannes Breuning, Marion H Brown
CD6 is a type I T cell surface receptor which modulates antigen receptor signalling. Its activity is regulated by binding of its membrane proximal domain (domain 3) to a cell surface ligand, CD166. CD6 monoclonal antibodies (mAbs) specific for the membrane distal domain (domain 1) perturb CD6 function including itolizumab (Alzumab™ ) which has reached the clinic for treatment of autoimmune disease. We characterised molecular and functional properties of several CD6 mAbs including itolizumab to define potential mechanisms of action...
May 17, 2018: Immunology
https://www.readbyqxmd.com/read/29772028/randomized-phase-i-trial-hiv-core-003-depletion-of-serum-amyloid-p-component-and-immunogenicity-of-dna-vaccination-against-hiv-1
#10
Nicola J Borthwick, Thirusha Lane, Nathifa Moyo, Alison Crook, Jung Min Shim, Ian Baines, Edmund G Wee, Philip N Hawkins, Julian D Gillmore, Tomáš Hanke, Mark B Pepys
BACKGROUND: The failure of DNA vaccination in humans, in contrast to its efficacy in some species, is unexplained. Observational and interventional experimental evidence suggests that DNA immunogenicity may be prevented by binding of human serum amyloid P component (SAP). SAP is the single normal DNA binding protein in human plasma. The drug (R)-1-[6-[(R)-2-carboxypyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC, miridesap), developed for treatment of systemic amyloidosis and Alzheimer's disease, depletes circulating SAP by 95-99%...
2018: PloS One
https://www.readbyqxmd.com/read/29772011/induction-of-influenza-specific-local-cd8-t-cells-in-the-respiratory-tract-after-aerosol-delivery-of-vaccine-antigen-or-virus-in-the-babraham-inbred-pig
#11
Katie Tungatt, Garry Dolton, Sophie B Morgan, Meriem Attaf, Anna Fuller, Thomas Whalley, Johanneke D Hemmink, Emily Porter, Barbara Szomolay, Maria Montoya, John A Hammond, John J Miles, David K Cole, Alain Townsend, Mick Bailey, Pierre J Rizkallah, Bryan Charleston, Elma Tchilian, Andrew K Sewell
There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume...
May 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29771629/brain-uptake-of-multivalent-and-multi-specific-dvd-ig-proteins-after-systemic-administration
#12
Denise Karaoglu Hanzatian, Annette Schwartz, Farid Gizatullin, Jamie Erickson, Kangwen Deng, Ruth Villanueva, Christopher Stedman, Cristina Harris, Tariq Ghayur, Andrew Goodearl
Therapeutic monoclonal antibodies and endogenous IgG antibodies show limited uptake into the central nervous system (CNS) due to the blood-brain barrier (BBB), which regulates and controls the selective and specific transport of both exogenous and endogenous materials to the brain. The use of natural transport mechanisms, such as receptor-mediated transcytosis (RMT), to deliver antibody therapeutics into the brain have been studied in rodents and monkeys. Recent successful examples include monovalent bispecific antibodies and mono- or bivalent fusion proteins; however, these formats do not have the capability to bind to both the CNS target and the BBB transport receptor in a bivalent fashion as a canonical antibody would...
May 17, 2018: MAbs
https://www.readbyqxmd.com/read/29770450/relationship-of-epitope-glycosylation-and-other-properties-of-blood-group-proteins-to-the-immunogenicity-of-blood-group-antigens
#13
John G Howe, Gary Stack
BACKGROUND: The intrinsic properties of polypeptide blood group antigens that determine their relative immunogenicities are unknown. Because size, composition, charge, dose, and epitope glycosylation affect the immunogenicity of other polypeptides, we examined whether similar properties were related to the immunogenicity of blood group antigens. STUDY DESIGN AND METHODS: Amino acid (AA) sequences of antithetical blood group antigens were searched for N- and O-glycosylation sites...
May 16, 2018: Transfusion
https://www.readbyqxmd.com/read/29770392/promotion-of-neurite-outgrowth-by-rationally-designed-ngf-%C3%AE-binding-peptide-nanofibers
#14
Zeynep Okur, Oya I Senturk, Canelif Yilmaz, Gulcihan Gulseren, Busra Mammadov, Mustafa O Guler, Ayse B Tekinay
Promotion of neurite outgrowth is an important limiting step for regeneration in nerve injury and depends strongly on the local expression of nerve growth factor (NGF). The rational design of bioactive materials is a promising approach for the development of novel therapeutic methods for nerve regeneration, and biomaterials capable of presenting NGF to nerve cells are especially suitable for this purpose. In this study, we show bioactive peptide amphiphile (PA) nanofibers capable of promoting neurite outgrowth by displaying high density binding epitopes for NGF...
May 17, 2018: Biomaterials Science
https://www.readbyqxmd.com/read/29770347/precision-tagging-a-novel-seamless-protein-tagging-by-combinational-use-of-type-ii-and-type-iis-restriction-endonucleases
#15
Zhen Xu, Yan-Ning Rui, John P Hagan, Dong H Kim
Protein tagging is a powerful tool for performing comprehensive analyses of the biological functions of a protein of interest owing to the existence of a wide variety of tags. It becomes indispensable in some cases, such as in tracking protein dynamics in a live cell or adding a peptide epitope due to the lack of optimal antibodies. However, efficiently integrating an array of tags into the gene of interest remains a challenge. Traditional DNA recombinant technology based on type II restriction endonucleases renders protein tagging tedious and inefficient as well as the introduction of an unwanted junction sequence...
February 5, 2018: Bio-protocol
https://www.readbyqxmd.com/read/29769722/bystander-cd8-t-cells-are-abundant-and-phenotypically-distinct-in-human-tumour-infiltrates
#16
Yannick Simoni, Etienne Becht, Michael Fehlings, Chiew Yee Loh, Si-Lin Koo, Karen Wei Weng Teng, Joe Poh Sheng Yeong, Rahul Nahar, Tong Zhang, Hassen Kared, Kaibo Duan, Nicholas Ang, Michael Poidinger, Yin Yeng Lee, Anis Larbi, Alexis J Khng, Emile Tan, Cherylin Fu, Ronnie Mathew, Melissa Teo, Wan Teck Lim, Chee Keong Toh, Boon-Hean Ong, Tina Koh, Axel M Hillmer, Angela Takano, Tony Kiat Hon Lim, Eng Huat Tan, Weiwei Zhai, Daniel S W Tan, Iain Beehuat Tan, Evan W Newell
Various forms of immunotherapy, such as checkpoint blockade immunotherapy, are proving to be effective at restoring T cell-mediated immune responses that can lead to marked and sustained clinical responses, but only in some patients and cancer types1-4 . Patients and tumours may respond unpredictably to immunotherapy partly owing to heterogeneity of the immune composition and phenotypic profiles of tumour-infiltrating lymphocytes (TILs) within individual tumours and between patients5,6 . Although there is evidence that tumour-mutation-derived neoantigen-specific T cells play a role in tumour control2,4,7-10 , in most cases the antigen specificities of phenotypically diverse tumour-infiltrating T cells are largely unknown...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29769533/structure-of-a-cleavage-independent-hiv-env-recapitulates-the-glycoprotein-architecture-of-the-native-cleaved-trimer
#17
Anita Sarkar, Shridhar Bale, Anna-Janina Behrens, Sonu Kumar, Shailendra Kumar Sharma, Natalia de Val, Jesper Pallesen, Adriana Irimia, Devan C Diwanji, Robyn L Stanfield, Andrew B Ward, Max Crispin, Richard T Wyatt, Ian A Wilson
Furin cleavage of the HIV envelope glycoprotein is an essential step for cell entry that enables formation of well-folded, native-like glycosylated trimers, releases constraints on the fusion peptide, and limits enzymatic processing of the N-glycan shield. Here, we show that a cleavage-independent, stabilized, soluble Env trimer mimic (BG505 NFL.664) exhibits a "closed-form", native-like, prefusion conformation akin to furin-cleaved Env trimers. The crystal structure of BG505 NFL.664 at 3.39 Å resolution with two potent bNAbs also identifies the full epitopes of PGV19 and PGT122 that target the receptor binding site and N332 supersite, respectively...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29769329/isolation-of-state-dependent-monoclonal-antibodies-against-the-12-transmembrane-domain-glucose-transporter-4-using-virus-like-particles
#18
David F Tucker, Jonathan T Sullivan, Kimberly-Anne Mattia, Christine R Fisher, Trevor Barnes, Manu N Mabila, Rona Wilf, Chidananda Sulli, Meghan Pitts, Riley J Payne, Moniquetta Hall, Duncan Huston-Paterson, Xiaoxiang Deng, Edgar Davidson, Sharon H Willis, Benjamin J Doranz, Ross Chambers, Joseph B Rucker
The insulin-responsive 12-transmembrane transporter GLUT4 changes conformation between an inward-open state and an outward-open state to actively facilitate cellular glucose uptake. Because of the difficulties of generating conformational mAbs against complex and highly conserved membrane proteins, no reliable tools exist to measure GLUT4 at the cell surface, follow its trafficking, or detect the conformational state of the protein. Here we report the isolation and characterization of conformational mAbs that recognize the extracellular and intracellular domains of GLUT4, including mAbs that are specific for the inward-open and outward-open states of GLUT4...
May 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29769288/targeted-complement-inhibition-salvages-stressed-neurons-and-inhibits-neuroinflammation-after-stroke-in-mice
#19
Ali Alawieh, E Farris Langley, Stephen Tomlinson
Ischemic stroke results from the interruption of blood flow to the brain resulting in long-term motor and cognitive neurological deficits, and it is a leading cause of death and disability. Current interventions focus on the restoration of blood flow to limit neuronal death, but these treatments have a therapeutic window of only a few hours and do not address post-stroke cerebral inflammation. The complement system, a component of the innate immune system, is activated by natural immunoglobulin M (IgM) antibodies that recognize neoepitopes expressed in the brain after ischemic stroke...
May 16, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29769138/geographic-distribution-and-molecular-analysis-of-porcine-reproductive-and-respiratory-syndrome-viruses-circulating-in-swine-farms-in-the-republic-of-korea-between-2013-and-2016
#20
Hyeonjeong Kang, Ji Eun Yu, Ji-Eun Shin, Areum Kang, Won-Il Kim, Changhee Lee, Jienny Lee, In-Soo Cho, Se-Eun Choe, Sang-Ho Cha
BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) causes devastating disease characterized by reproductive failure and respiratory problems in the swine industry. To understand the recent prevalence and genetic diversity of field PRRSVs in the Republic of Korea, open reading frames (ORFs) 5 and 7 of PRRSV field isolates from 631 PRRS-affected swine farms nationwide in 2013-2016 were analyzed along with 200 Korean field viruses isolated in 2003-2010, and 113 foreign field and vaccine strains...
May 16, 2018: BMC Veterinary Research
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