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Affinity maturation

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https://www.readbyqxmd.com/read/28207486/particle-based-delivery-of-the-hiv-envelope-protein
#1
Benedikt Asbach, Ralf Wagner
PURPOSE OF REVIEW: A major focus in HIV vaccine research is the development of suitable antigens that elicit broadly neutralizing antibody responses targeting HIV's envelope protein (Env). Delivery of Env in a repetitive manner on particle-based carriers allows higher avidity interactions and is therefore expected to efficiently engage B cells, thus leading to affinity maturation that results in superior antibody responses characterized by improved breadth, potency, and durability. This review summarizes current work that is evaluating diverse types of such particulate carriers for Env delivery...
February 15, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28202453/parenchymatous-cell-division-characterizes-the-fungal-cortex-of-some-common-foliose-lichens
#2
William B Sanders, Asunción de Los Ríos
PREMISE OF THE STUDY: Lichen-forming fungi produce diverse vegetative tissues, some closely resembling those of plants. Yet it has been repeatedly affirmed that none is a true parenchyma, in which cellular compartments are subdivided from all adjacent neighbors by cross walls adjoining older cross walls. METHODS: Using transmission electron microscopy (TEM), we tested this assumption by examining patterns of septum formation in the parenchyma-like cortex of three lichens of different phylogenetic affinities: Sticta canariensis, Leptogium cyanescens, and Endocarpon pusillum...
February 15, 2017: American Journal of Botany
https://www.readbyqxmd.com/read/28193885/essential-role-of-immobilized-chemokine-cxcl12-in-the-regulation-of-the-humoral-immune-response
#3
Aleksandr Barinov, Lingjie Luo, Pamela Gasse, Vannary Meas-Yedid, Emmanuel Donnadieu, Fernando Arenzana-Seisdedos, Paulo Vieira
Chemokines control the migration of a large array of cells by binding to specific receptors on cell surfaces. The biological function of chemokines also depends on interactions between nonreceptor binding domains and proteoglycans, which mediate chemokine immobilization on cellular or extracellular surfaces and formation of fixed gradients. Chemokine gradients regulate synchronous cell motility and integrin-dependent cell adhesion. Of the various chemokines, CXCL12 has a unique structure because its receptor-binding domain is distinct and does not overlap with the immobilization domains...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28179430/polydom-is-an-extracellular-matrix-protein-involved-in-lymphatic-vessel-remodeling
#4
Nanami Morooka, Sugiko Futaki, Ryoko Sato-Nishiuchi, Masafumi Nishino, Yuta Totani, Chisei Shimono, Itsuko Nakano, Hiroyuki Nakajima, Naoki Mochizuki, Kiyotoshi Sekiguchi
: Rationale: Lymphatic vasculature constitutes a second vascular system, essential for immune surveillance and tissue fluid homeostasis. Maturation of the hierarchical vascular structure, with a highly-branched network of capillaries and ducts, is crucial for its function. Environmental cues mediate the remodeling process, but the mechanism that underlies this process is largely unknown. Objective: Polydom (also called Svep1) is an extracellular matrix protein identified as a high-affinity ligand for integrin α9β1...
February 8, 2017: Circulation Research
https://www.readbyqxmd.com/read/28176338/effects-of-neonatal-17%C3%AE-ethinyloestradiol-exposure-on-female-paced-mating-behaviour-in-the-rat
#5
Chiaki Komine, Shingo Nakajima, Yasuhiko Kondo, Yasuyuki Horii, Midori Yoshida, Maiko Kawaguchi
Correct perinatal oestrogen levels are critical for sexual differentiation. For example, perinatal exposure to oestrogen causes masculinization and defeminization of the brain in female rats and also induces delayed effects after maturation characterized by early onset of abnormal oestrus cycling. However, the mechanisms underlying the above effects of oestrogen remain to be fully determined. 17α-ethinyloestradiol (EE), a common synthetic oestrogen widely used in oral contraceptives, binds specifically to oestrogen receptors...
February 8, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28164762/regulation-of-ion-channels-cellular-carriers-and-na-k-atpase-by-janus-kinase-3
#6
Mentor Sopjani, Shpëtim Thaçi, Berat Krasniqi, Miranda Selmonaj, Mark Rinnerthaler, Miribane Dërmaku-Sopjani
Janus kinase-3 (JAK3), a tyrosine kinase, is expressed in a variety of tissues, including the brain, and is involved in the signaling of cytokine receptors. JAK3 participates in numerous functions, among other the cell survival and proliferation, neuroprotection, apoptosis, as well as cellular response to hypoxia and ischemia-reperfusion. This kinase further contributes in the signaling of hematopoietic cell cytokine receptors, dendritic cells activation, maturation, and immune suppression as well as to cell volume regulation...
February 3, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28164605/association-of-mir-146a-rs2910164-and-mir-149-rs2292832-variants-with-susceptibility-to-type-2-diabetes
#7
Behnam Alipoor, Reza Meshkani, Hamid Ghaedi, Zohreh Sharifi, Ghodratollah Panahi, Taghi Golmohammadi
BACKGROUND: The deregulation of miRNAs has been implicated in the pathogenesis of type 2 diabetes (T2D). Single nucleotide polymorphisms (SNPs) located within the miRNA sequence could alter miRNA maturation and expression or change the binding affinity of miRNAs to their target mRNAs. In the present study we aimed to elucidate the possible association between the miR-146a rs2910164 and miR-149 rs2292832 variants with the susceptibility to T2D and its related metabolic traits in an Iranian population...
August 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28160624/murine-models-of-germinal-center-derived-lymphomas
#8
REVIEW
Parham Ramezani-Rad, Robert C Rickert
The germinal center (GC) reaction is an adaptive immune response to select B cells bearing high-affinity B cell receptors (BCRs) to undergo further differentiation into antibody-producing cells or memory B cells. To drive affinity maturation, (GC) B cells undergo rounds of hypermutation and rapid proliferation, which can enhance susceptibility to malignant transformation. Lymphomas frequently originate from GC B cells, but the etiology for most lymphoma subtypes is unknown. Work in the past decade has more fully documented the mutational landscape in lymphomas, but the impact of these genomic lesions is often difficult to ascertain...
February 1, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28154257/antibody-fragments-for-on-site-testing-of-cannabinoids-generated-via-in-vitro-affinity-maturation
#9
Izumi Morita, Hiroyuki Oyama, Mayumi Yasuo, Kazuhisa Matsuda, Kengo Katagi, Aya Ito, Hiroka Tatsuda, Hiroyuki Tanaka, Satoshi Morimoto, Norihiro Kobayashi
Law enforcement against illicit use of cannabis and related substances requires rapid, feasible, and reliable tools for on-site testing of cannabinoids. Notably, methods based on cannabinoid-specific antibodies enable efficient screening of multiple specimens. Antibody engineering may accelerate development of modern and robust testing systems. Here, we used in vitro affinity maturation to generate a single-chain Fv fragment (scFv) that recognizes with high affinity the psychoactive cannabinoid, Δ(9)-tetrahydrocannabinol (THC)...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28153782/rapid-de-novo-generation-of-antigen-specific-human-b-cells-with-expression-of-blimp-1-and-aid-by-in-vitro-immunization
#10
Xu Fang, Yue Tong, Hong Tian, Hongyu Ning, Xiangdong Gao, Wenbing Yao
In vitro immunization with antigens and cytokines triggers specific human B-cell response in short periods and is therefore superior to conventional in vivo immunization for antibody development. However, this new technology is limited by low efficiency, poor reproducibility, and requirement of pre-immunized lymphocytes. In this study, we demonstrate a novel method for de novo inducing antigen-specific human B cells in vitro. Unlike previous in vitro immunization of unfractionated PBMCs, we firstly optimized the conditions for inducing monocyte-derived dendritic cells (DCs) to efficiently capture, process, and present antigens...
January 30, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28149160/immune-characteristics-study-of-ag490-a-signal-pathway-inhibitor-in-eae-model-mice
#11
Zhihua Zhao, Zhifeng Mao, Junjie Yin, Yaqing Shu, Wei Qiu, Zhengqi Lu, Xueqiang Hu
Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination, axonal damage and progressive neurologic dysfunction in central nervous system (CNS). Many evidences show that B cells play an important role in the pathogenesis of MS. Follicular helper T cells (Tfh) secrete IL-21 to prompt the proliferation and differentiation of B cells in germinal center (GC) through clonal proliferation, somatic hypermutation, antibody class switching, antibody affinity maturation process. AG490 is a synthetic inhibitor to JAK-STAT signal pathway, which has been studied in inflammatory, tumor and autoimmune diseases...
February 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28145454/eugenol-prevents-amyloid-formation-of-proteins-and-inhibits-amyloid-induced-hemolysis
#12
Kriti Dubey, Bibin G Anand, Dolat Singh Shekhawat, Karunakar Kar
Eugenol has attracted considerable attention because of its potential for many pharmaceutical applications including anti-inflammatory, anti-tumorigenic and anti-oxidant properties. Here, we have investigated the effect of eugenol on amyloid formation of selected globular proteins. We find that both spontaneous and seed-induced aggregation processes of insulin and serum albumin (BSA) are significantly suppressed in the presence of eugenol. Isothermal titration calorimetric data predict a single binding site for eugenol-insulin complex confirming the affinity of eugenol for native soluble insulin species...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28143982/differential-binding-of-mitochondrial-transcripts-by-mrb8170-and-mrb4160-regulates-distinct-editing-fates-of-mitochondrial-mrna-in-trypanosomes
#13
Sameer Dixit, Michaela Müller-McNicoll, Vojtěch David, Kathi Zarnack, Jernej Ule, Hassan Hashimi, Julius Lukeš
: A dozen mRNAs are edited by multiple insertions and/or deletions of uridine residues in the mitochondrion of Trypanosoma brucei Several protein complexes have been implicated in performing this type of RNA editing, including the mitochondrial RNA-binding complex 1 (MRB1). Two paralogous novel RNA-binding proteins, MRB8170 and MRB4160, are loosely associated with the core MRB1 complex. Their roles in RNA editing and effects on target mRNAs are so far not well understood. In this study, individual-nucleotide-resolution UV-cross-linking and affinity purification (iCLAP) revealed a preferential binding of both proteins to mitochondrial mRNAs, which was positively correlated with their extent of editing...
January 31, 2017: MBio
https://www.readbyqxmd.com/read/28135270/optimal-sequential-immunization-can-focus-antibody-responses-against-diversity-loss-and-distraction
#14
Shenshen Wang
Affinity maturation is a Darwinian process in which B lymphocytes evolve potent antibodies to encountered antigens and generate immune memory. Highly mutable complex pathogens present an immense antigenic diversity that continues to challenge natural immunity and vaccine design. Induction of broadly neutralizing antibodies (bnAbs) against this diversity by vaccination likely requires multiple exposures to distinct but related antigen variants, and yet how affinity maturation advances under such complex stimulation remains poorly understood...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28134243/portal-protein-functions-akin-to-a-dna-sensor-that-couples-genome-packaging-to-icosahedral-capsid-maturation
#15
Ravi K Lokareddy, Rajeshwer S Sankhala, Ankoor Roy, Pavel V Afonine, Tina Motwani, Carolyn M Teschke, Kristin N Parent, Gino Cingolani
Tailed bacteriophages and herpesviruses assemble infectious particles via an empty precursor capsid (or 'procapsid') built by multiple copies of coat and scaffolding protein and by one dodecameric portal protein. Genome packaging triggers rearrangement of the coat protein and release of scaffolding protein, resulting in dramatic procapsid lattice expansion. Here, we provide structural evidence that the portal protein of the bacteriophage P22 exists in two distinct dodecameric conformations: an asymmetric assembly in the procapsid (PC-portal) that is competent for high affinity binding to the large terminase packaging protein, and a symmetric ring in the mature virion (MV-portal) that has negligible affinity for the packaging motor...
January 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28133804/immunologic-characteristics-of-hiv-infected-individuals-who-make-broadly-neutralizing-antibodies
#16
REVIEW
Persephone Borrow, M Anthony Moody
Induction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse variants of human immunodeficiency virus type 1 (HIV-1) is a key, as-yet-unachieved goal of prophylactic HIV-1 vaccine strategies. However, some HIV-infected individuals develop bnAbs after approximately 2-4 years of infection, enabling analysis of features of these antibodies and the immunological environment that enables their induction. Distinct subsets of CD4(+) T cells play opposing roles in the regulation of humoral responses: T follicular helper (Tfh) cells support germinal center formation and provide help for affinity maturation and the development of memory B cells and plasma cells, while regulatory CD4(+) (Treg) cells including T follicular regulatory (Tfr) cells inhibit the germinal center reaction to limit autoantibody production...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133802/antibody-virus-co-evolution-in-hiv-infection-paths-for-hiv-vaccine-development
#17
REVIEW
Mattia Bonsignori, Hua-Xin Liao, Feng Gao, Wilton B Williams, S Munir Alam, David C Montefiori, Barton F Haynes
Induction of HIV-1 broadly neutralizing antibodies (bnAbs) to date has only been observed in the setting of HIV-1 infection, and then only years after HIV transmission. Thus, the concept has emerged that one path to induction of bnAbs is to define the viral and immunologic events that occur during HIV-1 infection, and then to mimic those events with a vaccine formulation. This concept has led to efforts to map both virus and antibody events that occur from the time of HIV-1 transmission to development of bnAbs...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133799/human-ig-knockin-mice-to-study-the-development-and-regulation-of-hiv-1-broadly-neutralizing-antibodies
#18
REVIEW
Laurent Verkoczy, Frederick W Alt, Ming Tian
A major challenge for HIV-1 vaccine research is developing a successful immunization approach for inducing broadly neutralizing antibodies (bnAbs). A key shortcoming in meeting this challenge has been the lack of animal models capable of identifying impediments limiting bnAb induction and ranking vaccine strategies for their ability to promote bnAb development. Since 2010, immunoglobulin knockin (KI) technology, involving inserting functional rearranged human variable exons into the mouse IgH and IgL loci has been used to express bnAbs in mice...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28133793/genetic-and-structural-analyses-of-affinity-maturation-in-the-humoral-response-to-hiv-1
#19
REVIEW
Thomas B Kepler, Kevin Wiehe
Most broadly neutralizing antibodies (BNAbs) elicited in response to HIV-1 infection are extraordinarily mutated. One goal of HIV-1 vaccine development is to induce antibodies that are similar to the most potent and broad BNAbs isolated from infected subjects. The most effective BNAbs have very high mutation frequencies, indicative of the long periods of continual activation necessary to acquire the BNAb phenotype through affinity maturation. Understanding the mutational patterns that define the maturation pathways in BNAb development is critical to vaccine design efforts to recapitulate through vaccination the successful routes to neutralization breadth and potency that have occurred in natural infection...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28122734/hugh-davson-distinguished-lectureship-article-caveolins-and-cavins-in-the-trafficking-maturation-and-degradation-of-caveolae-implications-for-cell-physiology
#20
Anna R Busija, Hemal H Patel, Paul A Insel
Caveolins (Cavs) are ~20 kDa scaffolding proteins that assemble as oligomeric complexes in lipid raft domains to form caveolae, flask-shaped plasma membrane (PM) invaginations. Caveolae ("little caves") require lipid-lipid, protein-lipid, and protein-protein interactions that can modulate the localization, conformational stability, ligand affinity, effector specificity, and other functions of proteins that are partners of Cavs. Cavs are assembled into small oligomers in the endoplasmic reticulum (ER), transported to the Golgi for assembly with cholesterol and other oligomers, and then exported to the PM as an intact coat complex...
January 25, 2017: American Journal of Physiology. Cell Physiology
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