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Antigen affinity

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https://www.readbyqxmd.com/read/28337326/crystal-structures-of-erap2-complexed-with-inhibitors-reveal-pharmacophore-requirements-for-optimizing-inhibitor-potency
#1
Anastasia Mpakali, Petros Giastas, Rebecca Deprez-Poulain, Athanasios Papakyriakou, Despoina Koumantou, Ronan Gealageas, Sofia Tsoukalidou, Dionisios Vourloumis, Irene M Mavridis, Efstratios Stratikos, Emmanuel Saridakis
Endoplasmic reticulum aminopeptidase 2 assists with the generation of antigenic peptides for presentation onto Major Histocompatibility Class I molecules in humans. Recent evidence has suggested that the activity of ERAP2 may contribute to the generation of autoimmunity, thus making ERAP2 a possible pharmacological target for the regulation of adaptive immune responses. To better understand the structural elements of inhibitors that govern their binding affinity to the ERAP2 active site, we cocrystallized ERAP2 with a medium activity 3,4-diaminobenzoic acid inhibitor and a poorly active hydroxamic acid derivative...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28337196/salmonella-typhi-porins-ompc-and-ompf-are-potent-adjuvants-for-t-dependent-and-t-independent-antigens
#2
Marisol Pérez-Toledo, Nuriban Valero-Pacheco, Rodolfo Pastelin-Palacios, Cristina Gil-Cruz, Christian Perez-Shibayama, Mario A Moreno-Eutimio, Ingeborg Becker, Sonia Mayra Pérez-Tapia, Lourdes Arriaga-Pizano, Adam F Cunningham, Armando Isibasi, Laura C Bonifaz, Constantino López-Macías
Several microbial components, such as bacterial DNA and flagellin, have been used as experimental vaccine adjuvants because of their inherent capacity to efficiently activate innate immune responses. Likewise, our previous work has shown that the major Salmonella Typhi (S. Typhi) outer membrane proteins OmpC and OmpF (porins) are highly immunogenic protective antigens that efficiently stimulate innate and adaptive immune responses in the absence of exogenous adjuvants. Moreover, S. Typhi porins induce the expression of costimulatory molecules on antigen-presenting cells through toll-like receptor canonical signaling pathways...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28331856/the-immunogenicity-of-hla-class-ii-mismatches-the-predicted-presentation-of-nonself-allo-hla-derived-peptide-by-the-hla-dr-phenotype-of-the-recipient-is-associated-with-the-formation-of-dsa
#3
Vadim Jucaud
The identification of permissible HLA class II mismatches can prevent DSA in mismatched transplantation. The HLA-DR phenotype of recipients contributes to DSA formation by presenting allo-HLA-derived peptides to T-helper cells, which induces the differentiation of B cells into plasma cells. Comparing the binding affinity of self and nonself allo-HLA-derived peptides for recipients' HLA class II antigens may distinguish immunogenic HLA mismatches from nonimmunogenic ones. The binding affinities of allo-HLA-derived peptides to recipients' HLA-DR and HLA-DQ antigens were predicted using the NetMHCIIpan 3...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28329101/naturally-acquired-antibodies-target-the-glutamate-rich-protein-on-intact-merozoites-and-predict-protection-against-febrile-malaria
#4
Ikhlaq Hussain Kana, Bright Adu, Régis Wendpayangde Tiendrebeogo, Susheel Kumar Singh, Daniel Dodoo, Michael Theisen
Background.: Plasmodium species antigens accessible at the time of merozoite release are likely targets of biologically functional antibodies. Methods.: Immunoglobulin G (IgG) antibodies against intact merozoites were quantified in the plasma of Ghanaian children from a longitudinal cohort using a novel flow cytometry-based immunofluorescence assay. Functionality of these antibodies, as well as glutamate-rich protein (GLURP)-specific affinity-purified IgG from malaria hyperimmune Liberian adults, was assessed by the opsonic phagocytosis (OP) assay...
February 21, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28327987/pssmhcpan-a-novel-pssm-based-software-for-predicting-class-i-peptide-hla-binding-affinity
#5
Geng Liu, Dongli Li, Zhang Li, Si Qiu, Wenhui Li, Cheng-Chi Chao, Naibo Yang, Handong Li, Zhen Cheng, Xin Song, Le Cheng, Xiuqing Zhang, Jian Wang, Huanming Yang, Kun Ma, Yong Hou, Bo Li
Background: Predicting peptides binding affinity with human leukocyte antigen (HLA) is a crucial step in developing powerful antitumor vaccine for cancer immunotherapy. Currently available methods work quite well in predicting peptide binding affinity with HLA alleles such as HLA-A*0201, HLA-A*0101, and HLA-B*0702 in terms of sensitivity and specificity. However, quite a few types of HLA alleles that are present in majority of human populations including HLA-A*0202, HLA-A*0203, HLA-A*6802, HLA-B*5101, HLA-B*5301, HLA-B*5401 and HLA-B*5701 still cannot be predicted with satisfactory accuracy using currently available methods...
March 15, 2017: GigaScience
https://www.readbyqxmd.com/read/28322497/single-molecule-force-spectroscopy-to-compare-natural-versus-artificial-antibody-antigen-interaction
#6
Congzhou Wang, Rong Hu, Jeremiah J Morrissey, Evan D Kharasch, Srikanth Singamaneni
Biorecognition is central to various biological processes and finds numerous applications in virtually all areas of chemistry, biology, and medicine. Artificial antibodies, produced by imprinting synthetic polymers, are designed to mimic the biological recognition capability of natural antibodies, while exhibiting superior thermal, chemical, and environmental stability compared to their natural counterparts. The binding affinity of the artificial antibodies to their antigens characterizes the biorecognition ability of these synthetic nanoconstructs and their ability to replace natural recognition elements...
March 21, 2017: Small
https://www.readbyqxmd.com/read/28322160/an-efficient-transient-expression-system-for-enhancing-generation-of-monoclonal-antibodies-in-293-suspension-cells
#7
Guoquan Zhang, Jie Liu, Wanting Fan, Qianyi Chen, Bin Shi
BACKGROUND: Recombinant monoclonal antibodies (mAbs) are useful in research, diagnosis, and therapy. The increased demands of recombinant mAbs require efficient production systems. A variety of expression vectors have been developed for stable or transient production of mAb in mammalian cells. However, though a few commercial expression systems of mAbs can be listened, the high expense often impedes academia researches. METHODS: In this study, we described the development of a transient mammalian system based on a bicistronic vector, which contains internal ribosome entry site (IRES) and enhancer elements to express IgG1 light chain (LC) and heavy chain (HC) in one transcript...
March 20, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28321219/computational-model-reveals-limited-correlation-between-germinal-center-b-cell-subclone-abundancy-and-affinity-implications-for-repertoire-sequencing
#8
Polina Reshetova, Barbera D C van Schaik, Paul L Klarenbeek, Marieke E Doorenspleet, Rebecca E E Esveldt, Paul-Peter Tak, Jeroen E J Guikema, Niek de Vries, Antoine H C van Kampen
Immunoglobulin repertoire sequencing has successfully been applied to identify expanded antigen-activated B-cell clones that play a role in the pathogenesis of immune disorders. One challenge is the selection of the Ag-specific B cells from the measured repertoire for downstream analyses. A general feature of an immune response is the expansion of specific clones resulting in a set of subclones with common ancestry varying in abundance and in the number of acquired somatic mutations. The expanded subclones are expected to have BCR affinities for the Ag higher than the affinities of the naive B cells in the background population...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28320776/epigenomic-promoter-alterations-amplify-gene-isoform-and-immunogenic-diversity-in-gastric-adenocarcinoma
#9
Aditi Qamra, Manjie Xing, Nisha Padmanabhan, Jeffrey Jun Ting Kwok, Shenli Zhang, Xu Chang, Yan Shan Leong, Ai Ping Lee Lim, Qianqao Tang, WenFong Ooi, Joyce Suling Lin, Tannistha Nandi, Xiaosai Yao, Xuewen Ong, Minghui Lee, Su Ting Tay, Angie Tan Lay Keng, Erna Gondo Santoso, Cedric Chuan Young Ng, Alvin Ng, Apinya Jusakul, Duane Smoot, Hassan Ashktorab, Sun Young Rha, Khay Guan Yeoh, Wei Peng Yong, Pierce K H Chow, Weng Hoong Chan, Hock Soo Ong, Khee Chee Soo, Kyoung-Mee Kim, Wai Keong Wong, Steven G Rozen, Bin Tean Teh, Dennis Kappei, Jeeyun Lee, John Connolly, Patrick Tan
Promoter elements play important roles in isoform and cell-type specific expression. We surveyed the epigenomic promoter landscape of gastric adenocarcinoma (GC), analyzing 110 chromatin profiles (H3K4me3, H3K4me1, H3K27ac) of primary GCs, GC lines, and non-malignant gastric tissues. We identified ~2000 promoter alterations (somatic promoters), many deregulated in various epithelial malignancies and mapping frequently to alternative promoters within the same gene, generating potential pro-oncogenic isoforms (RASA3)...
March 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28320756/do-memory-b-cells-form-secondary-germinal-centers-it-depends
#10
Kathryn A Pape, Marc K Jenkins
The memory B-cell pool in an immune individual is more heterogeneous than previously recognized. The different types of memory B cells likely play distinct roles in tuning the secondary immune response because they differ in their potential to generate plasmablasts, which secrete antibodies, or germinal center (GC) cells, which generate new and higher affinity memory cells. We propose that the production of plasmablasts or GC cells by a memory B cell is controlled by its state of differentiation and the amount and affinity of antigen-specific antibodies present in the individual in which it resides...
March 20, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28319733/plasma-cell-and-memory-b-cell-differentiation-from-the-germinal-center
#11
REVIEW
Dan Suan, Christopher Sundling, Robert Brink
Germinal centers (GCs) form in secondary lymphoid tissues in response to antigenic challenge and are the site of somatic hypermutation, generating GC B cells with increasing affinity for the inciting agent that are positively selected over time. However, it is not until GC B cells differentiate into memory B cells and plasma cells and egress from the GC back into the circulation that effective long-lived humoral immunity is conferred upon the host. Here we review what is known about the signals that initiate the transition from a GC B cell into the memory B cell and plasma cell compartments and the downstream transcriptional regulation of these processes...
March 16, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319730/deconstructing-the-germinal-center-one-cell-at-a-time
#12
REVIEW
Chad R Dufaud, Louise J McHeyzer-Williams, Michael G McHeyzer-Williams
Successful vaccination relies on driving the immune response towards high specificity, affinity and longevity. Germinal centers facilitate the evolution of antigen-specific B cells by iterative rounds of diversification, selection, and differentiation to memory and plasma cells. Experimental evidence points to B cell receptor affinity and amount of antigen presented to follicular helper T cells as main drivers of clonal evolution. Concurrent studies suggest that modifiers of cognate contact, temporal mechanisms, and stochastic factors can also shape diversity and influence differentiation to memory and plasma cells, but molecular pathways driving these selection decisions are unresolved...
March 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28318221/crystal-structure-of-a-homogeneous-igg-fc-glycoform-with-the-n-glycan-designed-to-maximize-the-antibody-dependent-cellular-cytotoxicity
#13
Chia-Lin Chen, Jen-Chi Hsu, Chin-Wei Lin, Chia-Hung Wang, Ming-Hung Tsai, Chung-Yi Wu, Chi-Huey Wong, Che Ma
N-glycosylation on IgG modulates Fc conformation and effector functions. An IgG-Fc contains a human sialo-complex type (hSCT) glycan of biantennary structure with two α2,6-sialylations and without core-fucosylation is an optimized glycoform developed to enhance the antibody dependent cellular cytotoxicity (ADCC). hSCT modification not only enhances the binding affinity to Fc receptors in the presence of antigen, but also in some cases provides gain-of-function effector activity. We used enzymatic glyco-engineering to prepare an IgG-Fc with homogeneous hSCT attached to each CH2 domain, and solved its crystal structure...
March 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28316015/expression-and-characterization-of-codon-optimized-crimean-congo-hemorrhagic-fever-virus-gn-glycoprotein-in-insect-cells
#14
Mehdi Rahpeyma, Alireza Samarbaf-Zadeh, Manoochehr Makvandi, Ata A Ghadiri, Stuart D Dowall, Fatemeh Fotouhi
Crimean-Congo hemorrhagic fever virus (CCHFV) is a major cause of tick-borne viral hemorrhagic disease in the world. Despite of its importance as a deadly pathogen, there is currently no licensed vaccine against CCHF disease. The attachment glycoprotein of CCHFV (Gn) is a potentially important target for protective antiviral immune responses. To characterize the expression of recombinant CCHFV Gn in an insect-cell-based system, we developed a gene expression system expressing the full-length coding sequence under a polyhedron promoter in Sf9 cells using recombinant baculovirus...
March 18, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28303694/lutetium-177-psma-radionuclide-therapy-for-men-with-prostate-cancer-a-review-of-the-current-literature-and-discussion-of-practical-aspects-of-therapy
#15
REVIEW
Louise Emmett, Kathy Willowson, John Violet, Jane Shin, Ashley Blanksby, Jonathan Lee
Prostate-specific membrane antigen (PSMA) is a receptor on the surface of prostate cancer cells that is revolutionising the way we image and treat men with prostate cancer. New small molecule peptides with high-binding affinity for the PSMA receptor have allowed high quality, highly specific PET imaging, in addition to the development of targeted radionuclide therapy for men with prostate cancer. This targeted therapy for prostate cancer has, to date, predominately used Lutetium 177 (Lu) labelled PSMA peptides...
March 2017: Journal of Medical Radiation Sciences
https://www.readbyqxmd.com/read/28303164/adverse-drug-reactions-triggered-by-the-common-hla-b-57-01-variant-a-molecular-docking-study
#16
George Van Den Driessche, Denis Fourches
BACKGROUND: Human leukocyte antigen (HLA) surface proteins are directly involved in idiosyncratic adverse drug reactions. Herein, we present a structure-based analysis of the common HLA-B*57:01 variant known to be responsible for several HLA-linked adverse effects such as the abacavir hypersensitivity syndrome. METHODS: First, we analyzed three X-ray crystal structures involving the HLA-B*57:01 protein variant, the anti-HIV drug abacavir, and different co-binding peptides present in the antigen-binding cleft...
2017: Journal of Cheminformatics
https://www.readbyqxmd.com/read/28301944/orientation-and-characterization-of-immobilized-antibodies-for-improved-immunoassays-review
#17
Nicholas G Welch, Judith A Scoble, Benjamin W Muir, Paul J Pigram
Orientation of surface immobilized capture proteins, such as antibodies, plays a critical role in the performance of immunoassays. The sensitivity of immunodiagnostic procedures is dependent on presentation of the antibody, with optimum performance requiring the antigen binding sites be directed toward the solution phase. This review describes the most recent methods for oriented antibody immobilization and the characterization techniques employed for investigation of the antibody state. The introduction describes the importance of oriented antibodies for maximizing biosensor capabilities...
March 16, 2017: Biointerphases
https://www.readbyqxmd.com/read/28300559/expression-purification-and-in-vitro-refolding-of-the-recombinant-truncated-saposin-like-protein-2-antigen-for-development-of-diagnosis-of-human-fascioliasis
#18
Abolfazl Mirzadeh, Zarrintaj Valadkhani, Asiyeh Yoosefy, Jalal Babaie, Majid Golkar, Ahmad Reza Esmaeili Rastaghi, Elham Kazemi-Rad, Keyhan Ashrafi
Early diagnosis of fascioliasis is critical in prevention of injury to the liver and bile ducts. Saposin-like protein (FhSAP-2) is probably the most ideal antigen of Fasciola hepatica for development of ELISA kits. SAP-2 has a conserved tertiary structure containing three disulfide bonds and conformational epitopes. Therefore, antigenicity of SAP-2 is greatly depends on disulfide bond formation and proper folding. We produced the recombinant truncated SAP-2 (rtSAP-2) in the SHuffle® T7 and Rosetta strain of E...
March 11, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28291776/first-in-human-phase-1-of-ys110-a-monoclonal-antibody-directed-against-cd26-in-advanced-cd26-expressing-cancers
#19
Eric Angevin, Nicolas Isambert, Véronique Trillet-Lenoir, Benoit You, Jérôme Alexandre, Gérard Zalcman, Philippe Vielh, Françoise Farace, Fanny Valleix, Thomas Podoll, Yu Kuramochi, Itaru Miyashita, Osamu Hosono, Nam H Dang, Kei Ohnuma, Taketo Yamada, Yutaro Kaneko, Chikao Morimoto
BACKGROUND: YS110 is a humanised IgG1 monoclonal antibody with high affinity to the CD26 antigen. YS110 demonstrated preclinical anti-tumour effects without significant side effects. METHODS: This FIH study was designed to determine the maximal tolerated dose (MTD) and recommended phase 2 dose (RP2D) to assess the tolerance, pharmacokinetics (PK) and pharmacodynamics profiles of YS110 and preliminary efficacy. YS110 were initially administered intravenously once every 2 weeks (Q2W) for three doses and then, based on PK data, once every week (Q1W) for five doses in patients with CD26-expressing solid tumours...
March 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28291337/ultrasensitive-scaffold-dependent-protease-sensors-with-large-dynamic-range
#20
Viktor Stein, Masuda Nabi, Kirill Alexandrov
The rational construction of synthetic protein switches with pre-defined input-output parameters constitutes a key goal of synthetic biology with many potential applications ranging from metabolic engineering to diagnostics. Yet, generally applicable strategies to construct tailor-engineered protein switches have so far remained elusive. Here, we use SpyTag/SpyCatcher-mediated protein ligation to engineer modularly organized, scaffold-dependent protease sensors that exploit a combination of affinity targeting and protease-inducible protein-protein interactions...
March 14, 2017: ACS Synthetic Biology
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