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Antigen affinity

Stephanie Ascough, Suzanna Paterson, Christopher Chiu
Respiratory syncytial virus (RSV) and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to developing reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived...
2018: Frontiers in Immunology
João Crispim Encarnação, Tim Schulte, Adnane Achour, Hanna Björkelund, Karl Andersson
Time-resolved analysis assays of receptor-ligand interactions are fundamental in basic research and drug discovery. Adequate methods are well developed for the analysis of recombinant proteins such as antibody-antigen interactions. However, assays for time-resolved ligand-binding processes on living cells are still rare, in particular within microbiology. In this report, the real-time cell-binding assay (RT-CBA) technology LigandTracer®, originally designed for mammalian cell culture, was extended to cover Gram-positive and Gram-negative bacteria...
March 17, 2018: Applied Microbiology and Biotechnology
Freja Aksel Jacobsen, Alexander N Scherer, Jeppe Mouritsen, Hera Bragadóttir, B Thomas Bäckström, Samra Sardar, Dan Holmberg, Anthony J Koleske, Åsa Andersson
Multiple sclerosis is a neuroinflammatory degenerative disease, caused by activated immune cells infiltrating the CNS. The disease etiology involves both genetic and environmental factors. The mouse genetic locus, Eae27, linked to disease development in the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis, was studied in order to identify contributing disease susceptibility factors and potential drug targets for multiple sclerosis. Studies of an Eae27 congenic mouse strain, revealed that genetic variation within Eae27 influences EAE development...
March 17, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
K M Okoniewska, A E Kedzierska, J Okoniewski, A Slawek, K Grzymajlo, A Chelmonska-Soyta, T Grabowski
Epitopes of regulatory T cells (tregitopes) represent linear sequences of amino acids that induce CD4+ CD25+ Foxp3+ T lymphocytes expansion both in vitro and in vivo. The tregitopes' effectiveness was confirmed in autoimmune disease mouse models and in murine transplant models. Therefore, tregitopes together with regulatory T cells (Tregs) could play a major role in maintaining immune tolerance. The purpose of the presented study was a selection of potential tregitopes and assessment of their impact on Tregs expansion...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Jae-Il Lee, Yun-Jung Choi, Hi-Jung Park, Kyeong Cheon Jung, Seong Hoe Park
Antibody formation against therapeutic agents, such as tumor necrosis factor inhibitors and Factor VIII, that leads to treatment failure has become a major challenge in the treatment of rheumatoid arthritis and hemophilia. It is well known that anti-CD154 antibodies have the highest potential to inhibit these types of adverse immune responses. Nevertheless, the formation of thromboemboli is the major hurdle in the clinical application of these anti-CD154 blocking antibodies. For this, we attempted to derive an idea as to how this major complication can be eliminated...
March 16, 2018: Biochemical and Biophysical Research Communications
Aruto Sugiyama, Mitsuo Umetsu, Hikaru Nakazawa, Teppei Niide, Ryutaro Asano, Takamitsu Hattori, Izumi Kumagai
The cytotoxicity of T cell-recruiting antibodies with their potential to damage late-stage tumor masses is critically dependent on their structural and functional properties. Recently, we reported a semi-high-throughput process for screening highly cytotoxic small bispecific antibodies (i.e., diabodies). In the present study, we improved the high-throughput performance of this screening process by removing the protein purification stage and adding a stage for determining the concentrations of the diabodies in culture supernatant...
March 13, 2018: Journal of Bioscience and Bioengineering
Jeliazko R Jeliazkov, Adnan Sljoka, Daisuke Kuroda, Nobuyuki Tsuchimura, Naoki Katoh, Kouhei Tsumoto, Jeffrey J Gray
Antibodies can rapidly evolve in specific response to antigens. Affinity maturation drives this evolution through cycles of mutation and selection leading to enhanced antibody specificity and affinity. Elucidating the biophysical mechanisms that underlie affinity maturation is fundamental to understanding B-cell immunity. An emergent hypothesis is that affinity maturation reduces the conformational flexibility of the antibody's antigen-binding paratope to minimize entropic losses incurred upon binding. In recent years, computational and experimental approaches have tested this hypothesis on a small number of antibodies, often observing a decrease in the flexibility of the complementarity determining region (CDR) loops that typically comprise the paratope and in particular the CDR-H3 loop, which contributes a plurality of antigen contacts...
2018: Frontiers in Immunology
Sara Bobisse, Raphael Genolet, Annalisa Roberti, Janos L Tanyi, Julien Racle, Brian J Stevenson, Christian Iseli, Alexandra Michel, Marie-Aude Le Bitoux, Philippe Guillaume, Julien Schmidt, Valentina Bianchi, Denarda Dangaj, Craig Fenwick, Laurent Derré, Ioannis Xenarios, Olivier Michielin, Pedro Romero, Dimitri S Monos, Vincent Zoete, David Gfeller, Lana E Kandalaft, George Coukos, Alexandre Harari
Immunotherapy directed against private tumor neo-antigens derived from non-synonymous somatic mutations is a promising strategy of personalized cancer immunotherapy. However, feasibility in low mutational load tumor types remains unknown. Comprehensive and deep analysis of circulating and tumor-infiltrating lymphocytes (TILs) for neo-epitope specific CD8+ T cells has allowed prompt identification of oligoclonal and polyfunctional such cells from most immunotherapy-naive patients with advanced epithelial ovarian cancer studied...
March 15, 2018: Nature Communications
Fatemeh Faraji, Nader Tajik, Mahdi Behdani, Mohammad Ali Shokrgozar, Amir Hassan Zarnani, Fatemeh Shahhosseini, Mahdi Habibi-Anbouhi
CD22 is a B-cell-specific trans-membrane glycoprotein which is found on the surface of the most B-cells and modulates their function, survival, and apoptosis. Recently, targeting this cell surface biomarker in B-cell malignancies and disorders has attracted a lot of attention. The variable domain of camelid single chain antibodies (VHH, Nanobody) is a form of antibodies with novel properties including small size (15-17 kDa), thermal and chemical stability, high affinity and homology to human antibody sequences...
March 15, 2018: Biotechnology and Applied Biochemistry
Hong Truong, Leonard G Gomella, Mathew L Thakur, Edouard J Trabulsi
PURPOSE: Current approaches to prostate cancer screening and diagnosis are plagued with limitations in diagnostic accuracy. There is a compelling need for biomolecular imaging that will not only detect prostate cancer early but also distinguish prostate cancer from benign lesions accurately. In this topic paper, we review evidence that supports further investigation of VPAC1-targeted PET/CT imaging in the primary diagnosis of prostate cancer. METHODS: A non-systematic review of Medline/PubMed was performed...
March 14, 2018: World Journal of Urology
Meike Hutt, Sina Fellermeier-Kopf, Oliver Seifert, Lisa C Schmitt, Klaus Pfizenmaier, Roland E Kontermann
Fusion proteins combining hexavalent TRAIL with antibody fragments allow for a targeted delivery and efficient apoptosis induction in tumor cells. Here, we analyzed scFv-Fc-scTRAIL molecules directed against EGFR, HER2, HER3, and EpCAM as well as an untargeted Fc-scTRAIL fusion protein for their potentials to induce cell death both in vitro and in a xenograft tumor model in vivo . The scFv-Fc-scTRAIL fusion protein directed against EGFR as well as the fusion protein directed against EpCAM showed targeting effects on the two tested colorectal carcinoma cell lines Colo205 and HCT116, while a fusion protein targeting HER3 was more effective than untargeted Fc-scTRAIL only on Colo205 cells...
February 16, 2018: Oncotarget
Maria Vono, Christiane Sigrid Eberhardt, Elodie Mohr, Floriane Auderset, Dennis Christensen, Mirco Schmolke, Rhea Coler, Andreas Meinke, Peter Andersen, Paul-Henri Lambert, Beatris Mastelic-Gavillet, Claire-Anne Siegrist
Neonates and infants are more vulnerable to infections and show reduced responses to vaccination. Consequently, repeated immunizations are required to induce protection and early life vaccines against major pathogens such as influenza are yet unavailable. Formulating antigens with potent adjuvants, including immunostimulators and delivery systems, is a demonstrated approach to enhance vaccine efficacy. Yet, adjuvants effective in adults may not meet the specific requirements for activating the early life immune system...
2018: Frontiers in Immunology
T K Aliev, I G Dement'eva, V A Toporova, V V Argentova, L P Pozdnyakova, M N Bokov, D A Dolgikh, P G Sveshnikov, M P Kirpichnikov
We obtained dimeric forms of IgA1- and IgA2m1-isotypes of FI6 antibody broadly specific to hemagglutinins of different subtypes of influenza A virus. It was shown that the dimers of IgA1 isotype are characterized by a higher antigen-binding activity compared to the IgA2m1 dimers. The affinity of IgA1 dimers to the strains of the H1N1 subtype is higher than that of the H3N2 subtype, which correlates with the properties of the parental human FI6 antibody.
January 2018: Doklady. Biochemistry and Biophysics
Emily C Sheppard, Rikke Brandstrup Morrish, Michael J Dillon, Rebecca Leyland, Richard Chahwan
Epigenetic modifications, such as histone modifications, DNA methylation status, and non-coding RNAs (ncRNA), all contribute to antibody maturation during somatic hypermutation (SHM) and class-switch recombination (CSR). Histone modifications alter the chromatin landscape and, together with DNA primary and tertiary structures, they help recruit Activation-Induced Cytidine Deaminase (AID) to the immunoglobulin (Ig) locus. AID is a potent DNA mutator, which catalyzes cytosine-to-uracil deamination on single-stranded DNA to create U:G mismatches...
2018: Frontiers in Immunology
Brian Luk, Yao Jiang, Jonathan Copp, Che-Ming J Hu, Nishta Krishnan, Weiwei Gao, Shulin Li, Ronnie H Fang, Liangfang Zhang
Within the body, cellular recognition is mediated in large part by receptor-ligand interactions that result from the surface marker expression of the participant cells. In the case of immune cells, these interactions can be highly specific, enabling them to carry out their protective functions in fighting off infection and malignancy. In this work, we demonstrate the biomimetic targeting of antigen-specific immune cell populations by using nanoparticles functionalized with natural membrane derived from cells expressing the cognate antigen...
March 13, 2018: Molecular Pharmaceutics
SangWook Lee, Jong Hyun Lee, Hyuck Gi Kwon, Thomas Laurell, Ok Chan Jeong, Soyoun Kim
Here, we report a sol-gel integrated affinity microarray for on-chip matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) that enables capture and identification of prostate?specific antigen (PSA) in samples. An anti-PSA antibody (H117) was mixed with a sol?gel, and the mixture was spotted onto a porous silicon (pSi) surface without additional surface modifications. The antibody easily penetrates the sol-gel macropore fluidic network structure, making possible high affinities...
2018: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
Sara Lago, Matteo Nadai, Monica Rossetto, Sara N Richter
BACKGROUND: G-quadruplexes (G4s) are nucleic acids secondary structures formed in guanine-rich sequences. Anti-G4 antibodies represent a tool for the direct investigation of G4s in cells. Surface Plasmon Resonance (SPR) is a high sensitive technology, suitable for assessing the affinity between biomolecules. We here aimed at improving the orientation of an anti-G4 antibody (1H6) on SPR sensor chip for optimizing the detection of binding antigens. METHODS: SPR was employed for the characterization of 1H6 interaction with G4 and non-G4 oligonucleotides...
March 7, 2018: Biochimica et Biophysica Acta
Abbas Shali, Sadegh Hasannia, Fatemeh Gashtasbi, S Masoud Abdous, S Shirin Shahangian, Shirin Jalili
Since anthrax is an acute infectious disease, detection and neutralization of the toxins of pathogenic Bacillus anthracis are of great importance. The critical role of protective antigen (PA) component of tripartite anthrax toxin in toxin entry into the host cell cytosol provided a great deal of effort to generate monoclonal antibodies against this constitute. Regarding the importance of anthrax detection/neutralization and unique physicochemical and pharmacological features of VHHs as single domain antibodies, the present study aimed to generate VHHs against the receptor binding domain of PA, termed PAD4...
March 7, 2018: International Journal of Biological Macromolecules
Mitsunori Shiroishi, Yuji Ito, Kenta Shimokawa, Jae Man Lee, Takahiro Kusakabe, Tadashi Ueda
Rheumatoid factors (RFs) are autoantibodies against the fragment-crystallizable (Fc) region of immunoglobulin G (IgG). In individuals with hematological diseases such as cryoglobulinemia and certain B-cell lymphoma forms, the RFs derived from specific heavy- and light-chain germline pairs, so-called "stereotypic RFs," are frequently produced in copious amounts and form immune complexes with IgG in serum. Of note, many structural details of the antigen-recognition mechanisms in RFs are unclear. Here, we report the crystal structure of the RF YES8c derived from the IGHV1-69/IGKV3-20 germline pair, the commonest of the stereotypic RFs, in complex with human IgG1-Fc at 2...
March 9, 2018: Journal of Biological Chemistry
Stanislav O Fedechkin, Natasha L George, Jacob T Wolff, Lawrence M Kauvar, Rebecca M DuBois
Respiratory syncytial virus (RSV) is a top cause of severe lower respiratory tract disease and mortality in young children and the elderly. The viral envelope G glycoprotein contributes to pathogenesis through its roles in host cell attachment and modulation of host immunity. Although the G glycoprotein is a target of protective RSV-neutralizing antibodies, its development as a vaccine antigen has been hindered by its heterogeneous glycosylation and sequence variability outside a conserved central domain (CCD)...
March 9, 2018: Science Immunology
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