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Antigen affinity

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https://www.readbyqxmd.com/read/28646705/identification-and-in-vitro-characterization-of-novel-nanobodies-against-human-granulocyte-colony-stimulating-factor-receptor-to-provide-inhibition-of-g-csf-function
#1
Hamid Bakherad, Seyed Latif Mousavi Gargari, Zargham Sepehrizadeh, Hossein Aghamollaei, Ramezan Ali Taheri, Maryam Torshabi, Mojtaba Tabatabaei Yazdi, Walead Ebrahimizadeh, Neda Setayesh
It has been shown that Granulocyte colony-stimulating factor (G-CSF) has a higher expression in malignant tumors, and anti-G-CSF therapy considerably decreases tumor growth, tumor vascularization and metastasis. Thus, blocking the signaling pathway of G-CSF could be beneficial in cancer therapy. This study is aimed at designing and producing a monoclonal nanobody that could act as an antagonist of G-CSF receptor. Nanobodies are the antigen binding fragments of camelid single-chain antibodies, also known as VHH...
June 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28644986/designing-novel-inhibitors-against-histone-acetyltransferase-hat-%C3%A2-gcn5-of-plasmodium-falciparum
#2
Amarjeet Kumar, Krishanu Bhowmick, Kunwar Somesh Vikramdeo, Neelima Mondal, Naidu Subbarao, Suman Kumar Dhar
During active proliferation phase of intra-erythrocytic cycle, the genome of P. falciparum is regulated epigenetically and evolutionary conserved parasite-specific histone proteins are extensively acetylated. The reversible process of lysine acetylation, causing transcriptional activation and its deacetylation, causing transcriptional repression is regulated by balanced activities of HATs and HDACs. They are also known to regulate antigenic variations and gametocytic conversion in P. falciparum. These histone modifying enzymes have been identified as potential targets for development of anitmalarials in literature...
June 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28641998/construction-of-a-hepatitis-b-virus-neutralizing-chimeric-monoclonal-antibody-recognizing-escape-mutants-of-the-viral-surface-antigen-hbsag
#3
Forough Golsaz-Shirazi, Mohammad Mehdi Amiri, Samira Farid, Motahareh Bahadori, Felix Bohne, Sebastian Altstetter, Lisa Wolff, Tohid Kazemi, Jalal Khoshnoodi, Mohammad Hojjat-Farsangi, Michael Chudy, Mahmood Jeddi-Tehrani, Ulrike Protzer, Fazel Shokri
Hepatitis B virus (HBV) infection is a global burden on the health-care system and is considered as the tenth leading cause of death in the world. Over 248 million patients are currently suffering from chronic HBV infection worldwide and annual mortality rate of this infection is 686000. The "a" determinant is a hydrophilic region present in all antigenic subtypes of hepatitis B surface antigen (HBsAg), and antibodies against this region can neutralize the virus and are protective against all subtypes. We have recently generated a murine anti-HBs monoclonal antibody (4G4), which can neutralize HBV infection in HepaRG cells and recognize most of the escape mutant forms of HBsAg...
June 19, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28641985/single-step-colony-assay-for-screening-antibody-libraries
#4
Mieko Kato, Yoshiro Hanyu
We describe a method, single-step colony assay, for simple and rapid screening of single-chain Fv fragment (scFv) libraries. Colonies of Escherichia coli expressing the scFv library are formed on a hydrophilic filter that is positioned in contact with a membrane coated with an antigen. scFv expression is triggered upon treatment of colonies with an induction reagent, following which scFvs are secreted from the cells and diffused to the antigen-coated membrane. scFvs that exhibit binding affinity for the antigen are captured by the membrane-immobilized antigen...
June 20, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28641561/induction-of-humoral-and-cellular-immune-responses-in-mice-by-multiepitope-vaccines-composing-of-both-t-and-b-lymphocyte-epitopes-of-mage-a3which-are-recombined-into-hbcag
#5
Qingxin Chen, Wenshu Li, Pengfei Wang, Huanyi Shao, Yujie Ding, Wenhuan Wang, Danwei Cen, Yiqi Cai, Xiangyang Xue, Lifang Zhang, Guanbao Zhu
MAGE-A3 is highly expressed in many kinds of malignant diseases, and considered to be an ideal candidate for anti-tumor vaccine. To improve the immunogenicity of epitopes of MAGE-A3, hepatitis B virus core antigen (HBcAg) was used as an immune-carrier by insertion epitopes at HBcAg major immunodominant region (HBcAg(MIR)). In present study, we designed three kinds of MAGE-A3 multiepitopes containing T and B-cell dominant epitope-rich peptides, and constructed three recombinant chimeras of HBcAg(MIR)/MAGE-A3(EPI-1), HBcAg(MIR)/MAGE-A3(EPI-2), and HBcAg(MIR)/MAGE-A3(EPI-3) with prokaryotic codon optimization...
June 20, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28639122/targeting-prostate-specific-membrane-antigen-psma-with-f-18-labeled-compounds-the-influence-of-prosthetic-groups-on-tumor-uptake-and-clearance-profile
#6
Vincent Bouvet, Melinda Wuest, Justin J Bailey, Cody Bergman, Nancy Janzen, John F Valliant, Frank Wuest
PURPOSE: Prostate-specific membrane antigen (PSMA) is an important biomarker expressed in the majority of prostate cancers. The favorable positron emission tomography (PET) imaging profile of the PSMA imaging agent 2-(3-(1-carboxy-5-[(6-[(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentane-dioic acid [(18)F]DCFPyL in preclinical prostate cancer models and in prostate cancer patients stimulated the development and validation of other fluorine-containing PSMA inhibitors to further enhance pharmacokinetics and simplify production methods...
June 21, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28636954/germinal-center-selection-and-affinity-maturation-require-dynamic-regulation-of-mtorc1-kinase
#7
Jonatan Ersching, Alejo Efeyan, Luka Mesin, Johanne T Jacobsen, Giulia Pasqual, Brian C Grabiner, David Dominguez-Sola, David M Sabatini, Gabriel D Victora
During antibody affinity maturation, germinal center (GC) B cells cycle between affinity-driven selection in the light zone (LZ) and proliferation and somatic hypermutation in the dark zone (DZ). Although selection of GC B cells is triggered by antigen-dependent signals delivered in the LZ, DZ proliferation occurs in the absence of such signals. We show that positive selection triggered by T cell help activates the mechanistic target of rapamycin complex 1 (mTORC1), which promotes the anabolic program that supports DZ proliferation...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636952/human-leukocyte-antigen-f-presents-peptides-and-regulates-immunity-through-interactions-with-nk-cell-receptors
#8
Charles L Dulberger, Curtis P McMurtrey, Angelique Hölzemer, Karlynn E Neu, Victor Liu, Adriana M Steinbach, Wilfredo F Garcia-Beltran, Michael Sulak, Bana Jabri, Vincent J Lynch, Marcus Altfeld, William H Hildebrand, Erin J Adams
Evidence is mounting that the major histocompatibility complex (MHC) molecule HLA-F (human leukocyte antigen F) regulates the immune system in pregnancy, infection, and autoimmunity by signaling through NK cell receptors (NKRs). We present structural, biochemical, and evolutionary analyses demonstrating that HLA-F presents peptides of unconventional length dictated by a newly arisen mutation (R62W) that has produced an open-ended groove accommodating particularly long peptides. Compared to empty HLA-F open conformers (OCs), HLA-F tetramers bound with human-derived peptides differentially stained leukocytes, suggesting peptide-dependent engagement...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28634816/critical-biological-parameters-modulate-affinity-as-a-determinant-of-function-in-t-cell-receptor-gene-modified-t-cells
#9
Timothy T Spear, Yuan Wang, Kendra C Foley, David C Murray, Gina M Scurti, Patricia E Simms, Elizabeth Garrett-Mayer, Lance M Hellman, Brian M Baker, Michael I Nishimura
T-cell receptor (TCR)-pMHC affinity has been generally accepted to be the most important factor dictating antigen recognition in gene-modified T-cells. As such, there is great interest in optimizing TCR-based immunotherapies by enhancing TCR affinity to augment the therapeutic benefit of TCR gene-modified T-cells in cancer patients. However, recent clinical trials using affinity-enhanced TCRs in adoptive cell transfer (ACT) have observed unintended and serious adverse events, including death, attributed to unpredicted off-tumor or off-target cross-reactivity...
June 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28634480/fc-galactosylation-of-human-immunoglobulin-gamma-isotypes-improves-c1q-binding-and-enhances-complement-dependent-cytotoxicity
#10
Benjamin Peschke, Christian W Keller, Patrick Weber, Isaak Quast, Jan D Lünemann
Binding of the complement component C1q to the CH2 domain of antigen-bound immunoglobulin gamma (IgG) activates the classical complement pathway and depends on its close proximity to Fc fragments of neighboring antibodies. IgG subclasses contain a highly conserved asparagine 297 (N)-linked biantennary glycan within their CH2 domains, the core structure of which can be extended with terminal galactose and sialic acid residues. To investigate whether Fc-glycosylation regulates effector functions of human IgG subclasses, we cloned the antigen-binding region of the CD20-specific monoclonal antibody rituximab into IgG isotype expression vectors...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28634215/vaccination-with-high-affinity-epitopes-impairs-antitumor-efficacy-by-increasing-pd-1expression-on-cd8-t-cells
#11
Christopher D Zahm, Viswa Colluru, Douglas G McNeel
Antitumor vaccines encoding self-antigens generally have low immunogenicity in clinical trials. Several approaches are aimed at improving vaccine immunogenicity, including efforts to alter encoded epitopes. Immunization with epitopes altered for increased affinity for the major histocompatibility complex (MHC) or T-cell receptor (TCR) elicits greater numbers of CD8 T cells but inferior antitumor responses. Our previous results suggested that programmed death 1 (PD-1) and its ligand (PD-L1) increased on antigen-specific CD8 T cells and tumor cells, respectively, after high-affinity vaccination...
June 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28630473/impact-of-antigen-density-on-the-binding-mechanism-of-igg-antibodies
#12
Maya Hadzhieva, Anastas D Pashov, Srinivas Kaveri, Sébastien Lacroix-Desmazes, Hugo Mouquet, Jordan D Dimitrov
The density and distribution pattern of epitopes at the surface of pathogens have a profound impact on immune responses. Although multiple lines of evidence highlight the significance of antigen surface density for antibody binding, a quantitative description of its effect on recognition mechanisms is missing. Here, we analyzed binding kinetics and thermodynamics of six HIV-1 neutralizing antibodies as a function of the surface density of envelope glycoprotein gp120. Antibodies that recognize gp120 with low to moderate binding affinity displayed the most pronounced sensitivity to variation in antigen density, with qualitative and substantial quantitative changes in the energetics of the binding process as revealed by non-equilibrium and equilibrium thermodynamic analyses...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630382/immunodiagnostic-value-of-echinococcus-granulosus-recombinant-b8-1-subunit-of-antigen-b
#13
Amir Savardashtaki, Bahador Sarkari, Farzane Arianfar, Zohreh Mostafavi-Pour
BACKGROUND: Cystic echinococcosis (CE), as a chronic parasitic disease, is a major health problem in many countries. The performance of the currently available serodiagnostic tests for the diagnosis of CE is unsatisfactory. OBJECTIVE: The current study aimed at sub-cloning a gene, encoding the B8/1 subunit of antigen B (AgB) from Echinococcus granulosus, using gene optimization for the immunodiagnosis of human CE. METHODS: The coding sequence for AgB8/1 subunit of Echinococcus granulosus was selected from GenBank and was gene-optimized...
June 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28630079/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-lessons-from-the-antibody-response-to-hiv-1
#14
Gabriel D Victora, Hugo Mouquet
Most broadly neutralizing antibodies to HIV-1 have in common an extreme degree of somatic hypermutation (SHM), which correlates with their ability to neutralize multiple viral strains. However, achieving such extreme SHM by immunization remains a challenge. Here, we discuss how antigenic variation during HIV-1 infection may work to exacerbate SHM by permitting multiple iterative cycles of affinity maturation in germinal centers, and speculate on how this could be recapitulated through vaccination.
June 19, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28630078/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-a-role-for-antibody-feedback
#15
Kai-Michael Toellner, Daniel M-Y Sze, Yang Zhang
We discuss the impact of antibody feedback on affinity maturation of B cells. Competition from epitope-specific antibodies produced earlier during the immune response leads to immune complex formation, which is essential for transport and deposition of antigen onto follicular dendritic cells (FDCs). It also reduces the concentration of free epitopes into the μm to nm range, which is essential for B-cell receptors (BCRs) to sense affinity-dependent changes in binding capacity. Antibody feedback may also induce epitope spreading, leading to a broader selection of epitopes recognized by newly emerging B-cell clones...
June 19, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28628608/tcp4-dependent-induction-of-constans-transcription-requires-gigantea-in-photoperiodic-flowering-in-arabidopsis
#16
Akane Kubota, Shogo Ito, Jae Sung Shim, Richard S Johnson, Yong Hun Song, Ghislain Breton, Greg S Goralogia, Michael S Kwon, Dianne Laboy Cintrón, Tomotsugu Koyama, Masaru Ohme-Takagi, Jose L Pruneda-Paz, Steve A Kay, Michael J MacCoss, Takato Imaizumi
Photoperiod is one of the most reliable environmental cues for plants to regulate flowering timing. In Arabidopsis thaliana, CONSTANS (CO) transcription factor plays a central role in regulating photoperiodic flowering. In contrast to posttranslational regulation of CO protein, still little was known about CO transcriptional regulation. Here we show that the CINCINNATA (CIN) clade of class II TEOSINTE BRANCHED 1/ CYCLOIDEA/ PROLIFERATING CELL NUCLEAR ANTIGEN FACTOR (TCP) proteins act as CO activators. Our yeast one-hybrid analysis revealed that class II CIN-TCPs, including TCP4, bind to the CO promoter...
June 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28627792/%C3%AE-catenin-in-desmoid-type-fibromatosis-deep-insights-on-the-role-of-t41a-and-s45f-mutations-on-protein-structure-and-gene-expression
#17
C Colombo, A Belfiore, N Paielli, L De Cecco, S Canevari, E Laurini, M Fermeglia, S Pricl, P Verderio, S Bottelli, M Fiore, S Stacchiotti, E Palassini, A Gronchi, S Pilotti, F Perrone
Desmoid- type fibromatosis (DF) is a rare mesenchymal lesion with high risk of local recurrence. Specific β-catenin mutations (S45F) appeared to be related to this higher risk compared to T41A mutated or wild type (WT). We explored the influence of both mutations and WT on structure stability and affinity of β-catenin for α-catenin and the pattern of gene expression that may influence DF behavior. Using 33 surgically resected primary DFs harboring T41A (n=14), S45F (n=10) or WT (n=9), we performed a comparative molecular analysis by protein/protein interaction modeling, gene expression by DASL microarrays, human inflammation gene panel and assessment of immune system-based biomarkers by immunohistochemistry...
June 19, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28623251/highly-functional-t-cell-receptor-repertoires-are-abundant-in-stem-memory-t-cells-and-highly-shared-among-individuals
#18
Takahiko Miyama, Takakazu Kawase, Kazutaka Kitaura, Ren Chishaki, Masashi Shibata, Kumi Oshima, Hiroshi Hamana, Hiroyuki Kishi, Atsushi Muraguchi, Kiyotaka Kuzushima, Hiroh Saji, Tadasu Shin-I, Ryuji Suzuki, Tatsuo Ichinohe
To expand our knowledge of the ontogeny of the T-cell receptor (TCR) repertoire of antigen-specific T-cell subsets, we combined next-generation deep sequencing and single-cell multiplex clonotype analysis to evaluate the diversity and frequency of paired TCRs, their functions and whether clonotypic TCRs are shared among different individuals. Using an HLA-A*02-restricted cytomegalovirus (CMV) pp65-derived immunogenic peptide, we found that the more dominant pp65-specific TCR clonotypes in the blood of healthy donors have higher binding affinities for the CMV peptide and arise from clonotypes that are highly shared among individuals...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622429/synthesis-and-antigenic-evaluation-of-oligosaccharide-mimics-of-vi-antigen-from-salmonella-typhi
#19
Xinshan Ye, Gao-Lan Zhang, Lin Yang, Jingjing Zhu
Salmonella typhi is responsible for typhoid fever, which is a serious health threat in developing countries. As a virulent factor of Salmonella typhi, the purified Vi polysaccharide (Vi PS) has become an effective vaccine to combat typhoid fever. The chemical synthesis can provide homogeneous and well-defined molecules for the development of Vi-based vaccines. However, the synthesis of Vi oligosaccharides in high yields and with exclusive α-stereoselectivities remains very challenging. In this paper, a series of Vi pseudooligosaccharides, including pseudo tetra-, hexa-, and octa-saccharides were efficiently synthesized...
June 16, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28619678/april-taci-axis-is-dispensable-for-the-immune-response-to-rabies-vaccination
#20
Shannon L Haley, Evgeni P Tzvetkov, Andrew G Lytle, Kishore R Alugupalli, Joseph R Plummer, James P McGettigan
There is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. To accomplish this goal, rabies virus (RABV)-based vaccines must rapidly activate B cells to secrete antibodies which neutralize pathogenic RABV before it enters the CNS. Increased understanding of how B cells effectively respond to RABV-based vaccines may improve efforts to simplify post-exposure prophylaxis (PEP) regimens...
June 12, 2017: Antiviral Research
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