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https://www.readbyqxmd.com/read/28944078/a-pore-forming-protein-implements-vlr-activated-complement-cytotoxicity-in-lamprey
#1
Fenfang Wu, Bo Feng, Yong Ren, Di Wu, Yue Chen, Shengfeng Huang, Shangwu Chen, Anlong Xu
Lamprey is a basal vertebrate with a unique adaptive immune system, which uses variable lymphocyte receptors (VLRs) for antigen recognition. Our previous study has shown that lamprey possessed a distinctive complement pathway activated by VLR. In this study, we identified a natterin family member-lamprey pore-forming protein (LPFP) with a jacalin-like lectin domain and an aerolysin-like pore-forming domain. LPFP had a high affinity with mannan and could form oligomer in the presence of mannan. LPFP could deposit on the surface of target cells, form pore-like complex resembling a wheel with hub and spokes, and mediate powerful cytotoxicity on target cells...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28942824/prediction-of-promiscuous-t-cell-epitopes-in-rna-dependent-rna-polymerase-of-chikungunya-virus
#2
Yasir Waheed, Sher Zaman Safi, Muzammil Hasan Najmi, Hafsa Aziz, Muhammad Imran
OBJECTIVE: To explore RNA dependent RNA polymerase of Chikungunya virus (CHIKV) and develop T cell based epitopes with high antigenicity and good binding affinity for the human leukocyte antigen (HLA) classes as targets for epitopes based CHIKV vaccine. METHODS: In this study we downloaded 371 non-structural protein 4 protein sequences of CHIKV belonging to different regions of the world from the US National Institute of Allergy and Infectious Diseases (NIAID) virus pathogen resource database...
August 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28942035/putative-role-of-kir3dl1-3ds1-alleles-and-hla-bw4-ligands-with-end-stage-renal-disease-and-long-term-renal-allograft-survival
#3
Swayam Prakash, Aditya Narayan Sarangi, Shahnawaz Alam, Avinash Sonawane, Raj Kumar Sharma, Suraksha Agrawal
BACKGROUND: Killer immunoglobulin receptors (KIR) are highly polymorphic in nature. KIR3DL1/3DS1 genes are known to affect HLA-B antigen binding affinity causing natural killer (NK) cell inhibition, which results into successful renal transplantation. In this study we have examined whether alleles of KIR3DL1/3DS1 play any role in changing the binding affinity with HLA-Bw4 antigen and if so then how are they associated with long term renal allograft survival. We have also evaluated plausible association of KIR3DL1 with HLA-A23/A24/A32 with renal pathophysiology...
September 20, 2017: Gene
https://www.readbyqxmd.com/read/28939548/icams-support-b-cell-interactions-with-t-follicular-helper-cells-and-promote-clonal-selection
#4
Irina Zaretsky, Ofir Atrakchi, Roei D Mazor, Liat Stoler-Barak, Adi Biram, Sara W Feigelson, Alexander D Gitlin, Britta Engelhardt, Ziv Shulman
The germinal center (GC) reaction begins with a diverse and expanded group of B cell clones bearing a wide range of antibody affinities. During GC colonization, B cells engage in long-lasting interactions with T follicular helper (Tfh) cells, a process that depends on antigen uptake and antigen presentation to the Tfh cells. How long-lasting T-B interactions and B cell clonal expansion are regulated by antigen presentation remains unclear. Here, we use in vivo B cell competition models and intravital imaging to examine the adhesive mechanisms governing B cell selection for GC colonization...
September 22, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28935768/the-microanatomic-segregation-of-selection-by-apoptosis-in-the-germinal-center
#5
Christian T Mayer, Anna Gazumyan, Ervin E Kara, Alexander D Gitlin, Jovana Golijanin, Charlotte Viant, Joy Pai, Thiago Y Oliveira, Qiao Wang, Amelia Escolano, Max Medina-Ramirez, Rogier W Sanders, Michel C Nussenzweig
B cells undergo rapid cell division and affinity maturation in anatomically distinct sites in lymphoid organs called germinal centers (GCs). Homeostasis is maintained in part by B cell apoptosis. However, the precise contribution of apoptosis to GC biology and selection is not well defined. We developed apoptosis-indicator mice and used them to visualize, purify, and characterize dying GC B cells. Apoptosis is prevalent in the GC with up to half of all GC B cells dying every 6 hours. Moreover, programmed cell death is differentially regulated in the light zone (LZ) and the dark zone (DZ): LZ B cells die by default if they are not positively selected, whereas DZ cells die when their antigen receptors are damaged by activation-induced cytidine deaminase (AID)...
September 21, 2017: Science
https://www.readbyqxmd.com/read/28933967/aid-biology-a-pathological-and-clinical-perspective
#6
Meenal Choudhary, Anubhav Tamrakar, Amit Kumar Singh, Monika Jain, Ankit Jaiswal, Prashant Kodgire
Activation-induced cytidine deaminase (AID), primarily expressed in activated mature B lymphocytes in germinal centers, is the key factor in adaptive immune response against foreign antigens. AID is responsible for producing high-affinity and high-specificity antibodies against an infectious agent, through the physiological DNA alteration processes of antibody genes by somatic hypermutation (SHM) and class-switch recombination (CSR) and functions by deaminating deoxycytidines (dC) to deoxyuridines (dU), thereby introducing point mutations and double-stranded chromosomal breaks (DSBs)...
September 21, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28933642/epitope-characterization-of-anti-jam-a-antibodies-using-orthogonal-mass-spectrometry-and-surface-plasmon-resonance-approaches
#7
Guillaume Terral, Thierry Champion, François Debaene, Olivier Colas, Maxime Bourguet, Elsa Wagner-Rousset, Nathalie Corvaia, Alain Beck, Sarah Cianferani
Junctional adhesion molecule-A (JAM-A) is an adherens and tight junction protein expressed by endothelial and epithelial cells and associated with cancer progression. We present here the extensive characterization of immune complexes involving JAM-A antigen and three monoclonal antibodies (mAbs), including hz6F4-2, a humanized version of anti-tumoral 6F4 mAb identified by a functional and proteomic approach in our laboratory. A specific workflow that combines orthogonal approaches has been designed to determine binding stoichiometries along with JAM-A epitope mapping determination at high resolution for these three mAbs...
September 21, 2017: MAbs
https://www.readbyqxmd.com/read/28932628/a-novel-in-silico-framework-to-improve-mhc-i-epitopes-and-break-the-tolerance-to-melanoma
#8
Cristian Capasso, Aniket Magarkar, Victor Cervera-Carascon, Manlio Fusciello, Sara Feola, Martin Muller, Mariangela Garofalo, Lukasz Kuryk, Siri Tähtinen, Lucio Pastore, Alex Bunker, Vincenzo Cerullo
Tolerance toward tumor antigens, which are shared by normal tissues, have often limited the efficacy of cancer vaccines. However, wild type epitopes can be tweaked to activate cross-reactive T-cell clones, resulting in antitumor activity. The design of these analogs (i.e., heteroclitic peptides) can be difficult and time-consuming since no automated in silico tools are available. Hereby we describe the development of an in silico framework to improve the selection of heteroclitic peptides. The Epitope Discovery and Improvement System (EDIS) was first validated by studying the model antigen SIINFEKL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932173/efficient-and-inexpensive-transient-expression-of-multispecific-multivalent-antibodies-in-expi293-cells
#9
Xiaotian T Fang, Dag Sehlin, Lars Lannfelt, Stina Syvänen, Greta Hultqvist
BACKGROUND: Immunotherapy is a very fast expanding field within drug discovery and, hence, rapid and inexpensive expression of antibodies would be extremely valuable. Antibodies are, however, difficult to express. Multifunctional antibodies with additional binding domains further complicate the expression. Only few protocols describe the production of tetravalent bispecific antibodies and all with limited expression levels.. METHODS: Here, we describe a protocol that can produce functional tetravalent, bispecific antibodies at around 22 mg protein/l to a low cost...
2017: Biological Procedures Online
https://www.readbyqxmd.com/read/28931470/free-light-chains-eclectic-multipurpose-biomarker
#10
REVIEW
Umberto Basile, Francesca Gulli, Laura Gragnani, Cecilia Napodano, Krizia Pocino, Gian Ludovico Rapaccini, Michele Mussap, Anna Linda Zignego
The production of antibodies is accompanied by a slight excess of synthesis of κ and λ immunoglobulin light chains; small amounts of them are released in the peripheral blood and can also be found in various body fluids, such as synovial fluid, cerebrospinal fluid, urine and saliva. They are rapidly filtered by the glomerulus and >99% are reabsorbed from the cells of the proximal convoluted tubule, making them present in the urine in only trace amounts. The production of an excess of protein without a reason or a specific function in a biological system is rare...
September 17, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28929019/heterologous-expression-of-plasmodium-vivax-apical-membrane-antigen-1-pvama1-for-binding-peptide-selection
#11
Ching Hoong Chew, Yvonne Ai Lian Lim, Kek Heng Chua
BACKGROUND: Plasmodium is an obligate intracellular parasite. Apical membrane antigen 1 (AMA1) is the most prominent and well characterized malarial surface antigen that is essential for parasite-host cell invasion, i.e., for sporozoite to invade and replicate within hepatocytes in the liver stage and merozoite to penetrate and replicate within erythrocytes in the blood stage. AMA1 has long served as a potent antimalarial drug target and is a pivotal vaccine candidate. A good understanding of the structure and molecular function of this Plasmodium protein, particularly its involvement in host-cell adhesion and invasion, is of great interest and hence it offers an attractive target for the development of novel therapeutics...
2017: PeerJ
https://www.readbyqxmd.com/read/28928732/facile-affinity-maturation-of-antibody-variable-domains-using-natural-diversity-mutagenesis
#12
Kathryn E Tiller, Ratul Chowdhury, Tong Li, Seth D Ludwig, Sabyasachi Sen, Costas D Maranas, Peter M Tessier
The identification of mutations that enhance antibody affinity while maintaining high antibody specificity and stability is a time-consuming and laborious process. Here, we report an efficient methodology for systematically and rapidly enhancing the affinity of antibody variable domains while maximizing specificity and stability using novel synthetic antibody libraries. Our approach first uses computational and experimental alanine scanning mutagenesis to identify sites in the complementarity-determining regions (CDRs) that are permissive to mutagenesis while maintaining antigen binding...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28921455/construction-of-an-hrp-streptavidin-bound-antigen-and-its-application-in-an-elisa-for-porcine-circovirus-2-antibodies
#13
Meng Ge, Run-Cheng Li, Tailong Qu, Wenjie Gong, Xing-Long Yu, Changchun Tu
A fusion protein SBP-Cap∆41, consisting of Cap∆41 (without 41 amino acids at the N-terminus) protein of porcine circovirus 2 (PCV2) and a streptavidin binding peptide (SBP), was constructed. This fusion protein binds to HRP-labeled streptavidin (HRP-SA) through high affinity between SBP and SA, forming an HRP-streptavidin bound antigen (Hsb-Ag) with both immunoreactivity and enzymatic activity, which can be used in a double-antigen sandwich ELISA for detection of PCV2 antibodies. Comparison of the characteristics of the HSb-Cap∆41 and chemical conjugates of the recombinant Cap∆41 protein showed that the HSb-Cap∆41 based double-antigen sandwich ELISA (HBDS-ELISA) had higher specificity and sensitivity...
September 18, 2017: AMB Express
https://www.readbyqxmd.com/read/28921442/preparation-of-immunoliposomes-by-direct-coupling-of-antibodies-based-on-a-thioether-bond
#14
Raquel Petrilli, Josimar O Eloy, Robert J Lee, Renata F V Lopez
Drug delivery is of paramount importance, since the drug needs to be delivered to a specific site, in adequate concentration, avoiding degradation in order to provide therapeutic efficacy. Different nanocarriers have been used over the years for this purpose and liposomes are well-established systems due to the high biocompatibility and the possibility to vehiculate both hydrophilic and lipophilic drugs. In order to circumvent the rapid clearance by the reticuloendothelial system and to avoid the healthy cells exposure to the drug, long circulating liposomes containing polyethyleneglycol (PEG) and functionalized liposomes for targeted delivery have been developed...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28919226/validation-of-hav-biomarker-2a-for-differential-diagnostic-of-hepatitis-a-infected-and-vaccinated-individuals-using-multiplex-serology
#15
Katrin Bohm, Angela Filomena, Nicole Schneiderhan-Marra, Gérard Krause, Claudia Sievers
BACKGROUND: Worldwide about 1.5 million clinical cases of hepatitis A virus (HAV) infections occur every year and increasingly countries are introducing HAV vaccination into the childhood immunization schedule with a single dose instead of the originally licenced two dose regimen. Diagnosis of acute HAV infection is determined serologically by anti-HAV-IgM detection using ELISA. Additionally anti-HAV-IgG can become positive during the early phase of symptoms, but remains detectable after infection and also after vaccination against HAV...
September 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28918052/a-ctla-4-antagonizing-dna-aptamer-with-antitumor-effect
#16
Bo-Tsang Huang, Wei-Yun Lai, Yi-Chung Chang, Jen-Wei Wang, Shauh-Der Yeh, Emily Pei-Ying Lin, Pan-Chyr Yang
The successful translation of cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade has revolutionized the concept of cancer immunotherapy. Although monoclonal antibody therapeutics remain the mainstream in clinical practice, aptamers are synthetic oligonucleotides that encompass antibody-mimicking functions. Here, we report a novel high-affinity CTLA-4-antagonizing DNA aptamer (dissociation constant, 11.84 nM), aptCTLA-4, which was identified by cell-based SELEX and high-throughput sequencing. aptCTLA-4 is relatively stable in serum, promotes lymphocyte proliferation, and inhibits tumor growth in cell and animal models...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28916524/new-methods-to-analyze-b-cell-immune-responses-to-thymus-dependent-antigen-sheep-red-blood-cells
#17
Ellen J McAllister, John R Apgar, Charlotte R Leung, Robert C Rickert, Julia Jellusova
B cells contribute critically to an effective immune response by producing Ag-specific Abs. During the immune response to so-called "thymus-dependent Ags," activated B cells seek T cell help and form germinal centers. In contrast, thymus-independent Ags generally do not induce germinal center formation. In the germinal center, B cells undergo somatic hypermutation, affinity-based clonal expansion, and differentiation to produce plasma cells and memory B cells. Valuable insight into these processes has been gained by using model hapten-carrier complexes or SRBCs...
September 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28914198/pemtb-a-database-of-mhc-antigenic-peptide-of-mycobacterium-tuberculosis
#18
Qamar Zia, Asim Azhar, Shadab Ahmad, Mohammad Afsar, Ziaul Hasan, Mohammad Owais, Mahfooz Alam, Shabab Akbar, Magdah Ganash, Ghulam Md Ashraf, Swaleha Zubair, Gjumrakch Aliev
BACKGROUND: For design of a subunit vaccine for tuberculosis, identification of antigenic T-cell epitope is of utmost importance. Several MHC prediction server are available that can accurately predict antigenic peptide of variable lengths. However, peptides predicted from one server not necessarily are predicted form another server, thus creating a confusing situation for scientists to choose a best epitope. METHOD: Keeping the above problem in mind, we developed a comprehensive database of peptides of Mycobacterial proteins...
September 14, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28912108/leptospira-borgpetersenii-hybrid-leucine-rich-repeat-protein-cloning-and-expression-immunogenic-identification-and-molecular-docking-evaluation
#19
Tepyuda Sritrakul, Supachai Nitipan, Worawidh Wajjwalku, Anchalee La-Ard, Chattip Suphatpahirapol, Wimol Petkarnjanapong, Boonsong Ongphiphadhanakul, Siriwan Prapong
Leptospirosis is an important zoonotic disease, and the major outbreak of this disease in Thailand in 1999 was due largely to the Leptospira borgpetersenii serovar Sejroe. Identification of the leucine-rich repeat (LRR) LBJ_2271 protein containing immunogenic epitopes and the discovery of the LBJ_2271 ortholog in Leptospira serovar Sejroe, KU_Sej_R21_2271, led to further studies of the antigenic immune properties of KU_Sej_LRR_2271. The recombinant hybrid (rh) protein was created and expressed from a hybrid PCR fragment of KU_Sej_R21_2271 fused with DNA encoding the LBJ_2271 signal sequence for targeting protein as a membrane-anchoring protein...
September 12, 2017: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/28904125/enhancing-vaccine-efficacy-by-engineering-a-complex-synthetic-peptide-to-become-a-super-immunogen
#20
Therése Nordström, Manisha Pandey, Ainslie Calcutt, Jessica Powell, Zachary N Phillips, Grace Yeung, Ashwini K Giddam, Yun Shi, Thomas Haselhorst, Mark von Itzstein, Michael R Batzloff, Michael F Good
Peptides offer enormous promise as vaccines to prevent and protect against many infectious and noninfectious diseases. However, to date, limited vaccine efficacy has been reported and none have been licensed for human use. Innovative ways to enhance their immunogenicity are being tested, but rational sequence modification as a means to improve immune responsiveness has been neglected. Our objective was to establish a two-step generic protocol to modify defined amino acids of a helical peptide epitope to create a superior immunogen...
September 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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