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T cell affinity

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https://www.readbyqxmd.com/read/28546465/quantitative-mass-spectrometry-analysis-of-pd-l1-protein-expression-n-glycosylation-and-expression-stoichiometry-with-pd-1-and-pd-l2-in-human-melanoma
#1
Carlos A Morales-Betanzos, Hyoungjoo Lee, Paula I Gonzalez-Ericsson, Justin M Balko, Douglas B Johnson, Lisa J Zimmerman, Daniel C Liebler
Quantitative assessment of key proteins that control the tumor-immune interface is one of the most formidable analytical challenges in immunotherapeutics. We developed a targeted mass spectrometry (MS) platform to quantify programmed cell death-1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2) at fmol/microgram protein levels in formalin fixed, paraffin-embedded sections from 22 human melanomas. PD-L1 abundance ranged 50-fold, from approximately 0.03 to 1.5 fmol/microgram protein and the PRM data were largely concordant with total PD-L1-positive cell content, as analyzed by immunohistochemistry (IHC) with the E1L3N antibody...
May 25, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28544366/enumeration-of-wt1-specific-cd8-t-cells-for-clinical-application-using-an-mhc-streptamer-based-no-wash-single-platform-flow-cytometric-assay
#2
Sarah Matko, Madeleine Teichert, Antje Tunger, Marc Schmitz, Martin Bornhauser, Torsten Tonn, Marcus Odendahl
The advent of novel strategies to generate leukemia-associated-antigen (LAA)-specific T cells for adoptive immunotherapies creates a demand for standardized good laboratory practice (GLP)-compliant enumeration assays to provide a secure clinical environment-whether it is to identify potential donors, define therapeutic doses for transplantation, or monitor clinical success. Here, we introduce a no-wash assay based on single-platform cell enumeration and Streptamer staining to determine the Wilms' tumor antigen 1 (WT1)-specific T cell immunity in clinical samples...
May 25, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28542541/varicella-zoster-virus-glycoprotein-c-increases-chemokine-mediated-leukocyte-migration
#3
Víctor González-Motos, Carina Jürgens, Birgit Ritter, Kai A Kropp, Verónica Durán, Olav Larsen, Anne Binz, Werner J D Ouwendijk, Tihana Lenac Rovis, Stipan Jonjic, Georges M G M Verjans, Beate Sodeik, Thomas Krey, Rudolf Bauerfeind, Thomas F Schulz, Benedikt B Kaufer, Ulrich Kalinke, Amanda E I Proudfoot, Mette M Rosenkilde, Abel Viejo-Borbolla
Varicella zoster virus (VZV) is a highly prevalent human pathogen that establishes latency in neurons of the peripheral nervous system. Primary infection causes varicella whereas reactivation results in zoster, which is often followed by chronic pain in adults. Following infection of epithelial cells in the respiratory tract, VZV spreads within the host by hijacking leukocytes, including T cells, in the tonsils and other regional lymph nodes, and modifying their activity. In spite of its importance in pathogenesis, the mechanism of dissemination remains poorly understood...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28541562/dna-substrate-recognition-and-processing-by-the-full-length-human-upf1-helicase
#4
Saba Dehghani-Tafti, Cyril M Sanders
UPF1 is a conserved helicase required for nonsense-mediated decay (NMD) regulating mRNA stability in the cytoplasm. Human UPF1 (hUPF1) is also needed for nuclear DNA replication. While loss of NMD is tolerated, loss of hUPF1 induces a DNA damage response and cell cycle arrest. We have analysed nucleic acid (NA) binding and processing by full-length hUPF1. hUPF1 unwinds non-B and B-form DNA and RNA substrates in vitro. Unlike many helicases involved in genome stability no hUPF1 binding to DNA structures stabilized by inter-base-pair hydrogen bonding was observed...
May 24, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28541550/integrity-of-immunoglobulin-variable-region-is-supported-by-ganp-during-aid-induced-somatic-hypermutation-in-germinal-center-b-cells
#5
Mohammed Mansour Abbas Eid, Mayuko Shimoda, Shailendra Kumar Singh, Sarah Ameen Almofty, Phuong Pham, Myron F Goodman, Kazuhiko Maeda, Nobuo Sakaguchi
Immunoglobulin (Ig) affinity maturation depends on somatic hypermutation (SHM) in variable (V) regions initiated by activation-induced cytidine deaminase (AID). AID induces transition mutations by C→U deamination on both strands, causing C:G→T:A. Error-prone repairs of U by base excision and mismatch repairs create transversion mutations at C/G and mutations at A/T sites. In Neuberger's model, it remained to clarify how transition/transversion repair is regulated. We investigate role of AID-interacting GANP (germinal-center associated nuclear protein) in IgV SHM profile...
May 24, 2017: International Immunology
https://www.readbyqxmd.com/read/28539189/the-individual-and-population-genetics-of-antibody-immunity
#6
REVIEW
Corey T Watson, Jacob Glanville, Wayne A Marasco
Antibodies (Abs) produced by immunoglobulin (IG) genes are the most diverse proteins expressed in humans. While part of this diversity is generated by recombination during B-cell development and mutations during affinity maturation, the germ-line IG loci are also diverse across human populations and ethnicities. Recently, proof-of-concept studies have demonstrated genotype-phenotype correlations between specific IG germ-line variants and the quality of Ab responses during vaccination and disease. However, the functional consequences of IG genetic variation in Ab function and immunological outcomes remain underexplored...
May 20, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28536262/in-silico-and-cell-based-analyses-reveal-strong-divergence-between-prediction-and-observation-of-t-cell-recognized-tumor-antigen-t-cell-epitopes
#7
Julien Schmidt, Philippe Guillaume, Danijel Dojcinovic, Julia Karbach, George Coukos, Immanuel Luescher
Tumor exomes provide comprehensive information on mutated, over-expressed genes and aberrant splicing, which can be exploited for personalized cancer immunotherapy. Of particular interest are mutated tumor antigen T cell epitopes, because neoepitope specific T cells often are tumoricidal. However, identifying tumor-specific T cell epitopes is a major challenge. A widely used strategy relies on initial prediction of human leukocyte antigen binding peptides by in silico algorithms, but the predictive power of this approach is unclear...
May 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28534196/in-silico-analysis-of-shiga-toxins-stxs-to-identify-new-potential-vaccine-targets-for-shiga-toxin-producing-escherichia-coli
#8
Maryam Golshani, Mana Oloomi, Saeid Bouzari
Shiga toxins belong to a family of structurally and functionally related toxins serving as the main virulence factors for pathogenicity of the Shiga toxin-producing Escherichia coli (STEC) associating with Hemolytic uremic syndrome (HUS). At present, there is no effective treatment or prevention for HUS. The aim of the present study was to find conserved regions within the amino acid sequences of Stx1, Stx2 (Shiga toxin) and their variants. In this regard, In-silico identification of conformational continuous B cell and T-cell epitopes was performed in order to introduce new potential vaccine candidates...
December 2016: In Silico Pharmacology
https://www.readbyqxmd.com/read/28533942/hla-a24-ligandome-analysis-of-colon-and-lung-cancer-cells-identifies-a-novel-cancer-testis-antigen-and-a-neoantigen-that-elicits-specific-and-strong-ctl-responses
#9
Vitaly Kochin, Takayuki Kanaseki, Serina Tokita, Sho Miyamoto, Yosuke Shionoya, Yasuhiro Kikuchi, Daichi Morooka, Yoshihiko Hirohashi, Tomohide Tsukahara, Kazue Watanabe, Shingo Toji, Yasuo Kokai, Noriyuki Sato, Toshihiko Torigoe
This study focused on HLA-A24 and comprehensively analyzed the ligandome of colon and lung cancer cells without the use of MHC-binding in silico prediction algorithms. Affinity purification using the antibody specific to HLA-A24 followed by LC-MS/MS sequencing was used to detect peptides, which harbored the known characteristics of HLA-A24 peptides in terms of length and anchor motifs. Ligandome analysis demonstrated the natural presentation of two different types of novel tumor-associated antigens. The ligandome contained a peptide derived from SUV39H2, a gene found to be expressed in a variety of cancers but not in normal tissues (except for the testis)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28533272/chimeric-pd-1-28-receptor-upgrades-low-avidity-t-cells-and-restores-effector-function-of-tumor-infiltrating-lymphocytes-for-adoptive-cell-therapy
#10
Ramona Schlenker, Luis Felipe Olguín-Contreras, Matthias Leisegang, Julia Schnappinger, Anja Disovic, Svenja Rühland, Peter J Nelson, Heinrich Leonhardt, Hartmann Harz, Susanne Wilde, Dolores J Schendel, Wolfgang Uckert, Gerald Willimsky, Elfriede Noessner
Inherent intermediate-to-low affinity T cell receptors (TCR) that develop during the natural course of immune responses may not allow sufficient activation for tumor elimination, making the majority of T cells suboptimal for adoptive T cell therapy (ATT). TCR affinity enhancement has been implemented to provide stronger T cell activity but carries the risk of creating undesired cross-reactivity leading to potential serious adverse effects in clinical application. We demonstrate here that engineering of low-avidity T cells recognizing a naturally processed and presented tumor-associated antigen with a chimeric PD-1:28 receptor increases effector function to levels seen with high-avidity T cells of identical specificity...
May 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28530569/binding-selectivity-of-dietary-polyphenols-to-different-plant-cell-wall-components-quantification-and-mechanism
#11
Anh Dao T Phan, Bernadine M Flanagan, Bruce R D'Arcy, Michael J Gidley
Selected polyphenols exhibited binding selectivity to different cellulose-based composites and apple cell walls. For catechin, cellulose is the dominant binding component, whereas hemicelluloses (xyloglucan and arabinoxylan) apparently did not contribute to polyphenol adsorption in the presence of cellulose. In contrast, ferulic acid and cyanidin-3-glucoside bound to cellulose-based composites and apple cell walls with different affinities, showing that both electrostatic interactions and plant cell wall microstructure were important...
October 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28529511/characterization-of-cd4-t-cell-epitopes-of-infliximab-and-rituximab-identified-from-healthy-donors
#12
Moustafa Hamze, Sylvain Meunier, Anette Karle, Abdelaziz Gdoura, Amélie Goudet, Natacha Szely, Marc Pallardy, Franck Carbonnel, Sebastian Spindeldreher, Xavier Mariette, Corinne Miceli-Richard, Bernard Maillère
The chimeric antibodies anti-CD20 rituximab (Rtx) and anti-TNFα infliximab (Ifx) induce antidrug antibodies (ADAs) in many patients with inflammatory diseases. Because of the key role of CD4 T lymphocytes in the initiation of antibody responses, we localized the CD4 T cell epitopes of Rtx and Ifx. With the perspective to anticipate immunogenicity of therapeutic antibodies, identification of the CD4 T cell epitopes was performed using cells collected in healthy donors. Nine T cell epitopes were identified in the variable chains of both antibodies by deriving CD4 T cell lines raised against either Rtx or Ifx...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28526683/autoreactivity-to-sulfatide-by-human-invariant-nkt-cells
#13
Annelein M Stax, Jessica Tuengel, Enrico Girardi, Naoki Kitano, Lenka L Allan, Victor Liu, Dongjun Zheng, William J Panenka, Joren Guillaume, Chi-Huey Wong, Serge van Calenbergh, Dirk M Zajonc, Peter van den Elzen
Invariant NKT (iNKT) cells are innate-like lymphocytes that recognize lipid Ags presented by CD1d. The prototypical Ag, α-galactosylceramide, strongly activates human and mouse iNKT cells, leading to the assumption that iNKT cell physiology in human and mouse is similar. In this article, we report the surprising finding that human, but not mouse, iNKT cells directly recognize myelin-derived sulfatide presented by CD1d. We propose that sulfatide is recognized only by human iNKT cells because of the unique positioning of the 3-O-sulfated β-galactose headgroup...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28524659/synthesis-molecular-docking-molecular-dynamics-studies-and-biological-evaluation-of-4h-chromone-1-2-3-4-tetrahydropyrimidine-5-carboxylate-derivatives-as-potential-antileukemic-agents
#14
Zahra Dolatkhah, Shahrzad Javanshir, Ahmad Shahir Sadr, Jaber Hosseini, Soroush Sardari
A series of 4H-chromone-1,2,3,4-tetrahydropyrimidine-5-carboxylates derivatives were synthesized via a three component one-pot condensation of chromone-3-carbaldehyde, alkyl acetoacetate, and urea or thiourea, using MCM-41-SO3H as efficient nanocatalysts and evaluated for their anticancer activity using a combined in silico docking and molecular dynamics protocol to estimate the binding affinity of the title compounds with the Bcr-Abl oncogene. Two programs, AutoDock 4 and AutoDock Vina software were applied to dock the target protein with synthesized compounds and ATP...
May 25, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28521290/mir-2964a-5p-binding-site-snp-regulates-atm-expression-contributing-to-age-related-cataract-risk
#15
Han Rong, Shanshan Gu, Guowei Zhang, Lihua Kang, Mei Yang, Junfang Zhang, Xinyue Shen, Huaijin Guan
This study was to explore the involvement of DNA repair genes in the pathogenesis of age-related cataract (ARC). We genotyped nine single nucleotide polymorphisms (SNPs) of genes responsible to DNA double strand breaks (DSBs) in 804 ARC cases and 804 controls in a cohort of eye diseases in Chinese population and found that the ataxia telangiectasia mutated (ATM) gene-rs4585:G>T was significantly associated with ARC risk. An in vitro functional test found that miR-2964a-5p specifically down-regulated luciferase reporter expression and ATM expression in the cell lines transfected with rs4585 T allele compared to rs4585 G allele...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28516165/host-and-pathogen-derived-adjuvant-coatings-on-protein-nanoparticle-vaccines
#16
Timothy Z Chang, Ishatou Diambou, Jong Rok Kim, Baozhong Wang, Julie A Champion
Nanoparticulate and molecular adjuvants have shown great efficacy in enhancing immune responses, and the immunogenic vaccines of the future will most likely contain both. To investigate the immunostimulatory effects of molecular adjuvants on nanoparticle vaccines, we have designed ovalbumin (OVA) protein nanoparticles coated with two different adjuvants-flagellin (FliC) and immunoglobulin M (IgM). These proteins, derived from Salmonella and mice, respectively, are representatives of pathogen- and host-derived molecules that can enhance immune responses...
March 2017: Bioengineering & Translational Medicine
https://www.readbyqxmd.com/read/28515322/g%C3%AE-%C3%AE-directly-modulates-vesicle-fusion-by-competing-with-synaptotagmin-for-binding-to-neuronal-snare-proteins-embedded-in-membranes
#17
Zack Zurawski, Brian Page, Michael C Chicka, Rebecca L Brindley, Christopher A Wells, Anita M Preininger, Karren Hyde, James A Gilbert, Osvaldo Cruz-Rodriguez, Kevin P M Currie, Edwin R Chapman, Simon Alford, Heidi E Hamm
Gi/o-coupled GPCRs can inhibit neurotransmitter release at synapses via multiple mechanisms. In addition to Gβγ-mediated modulation of voltage-gated calcium channels(VGCC), inhibition can also be mediated through the direct interaction of Gβγ subunits with the soluble N-ethylmaleimide attachment protein receptor (SNARE) complex of the vesicle fusion apparatus. Binding studies with soluble SNARE complexes have shown that Gβγ binds to both ternary SNARE complexes, t-SNARE heterodimers, and monomeric SNAREs, competing with synaptotagmin(syt)1 for binding sites on t-SNARE...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515320/recognition-of-nectin-2-by-the-natural-killer-cell-receptor-tigit
#18
Felix A Deuss, Benjamin S Gully, Jamie Rossjohn, Richard Berry
T cell immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed on the surface of natural killer (NK) cells. TIGIT recognizes nectin and nectin-like adhesion molecules and thus plays a critical role in the innate immune response to malignant transformation. While the TIGIT nectin-like protein-5 (necl-5) interaction is well understood, how TIGIT engages nectin-2, a receptor that is broadly over-expressed in breast and ovarian cancer, remains unknown. Here, we show that TIGIT bound to the immunoglobulin domain of nectin-2 that is most distal from the membrane with an affinity of 6 μM, which was moderately lower than the affinity observed for the TIGIT-necl-5 interaction (3...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28514446/identification-of-preoptic-sleep-neurons-using-retrograde-labelling-and-gene-profiling
#19
Shinjae Chung, Franz Weber, Peng Zhong, Chan Lek Tan, Thuc Nghi Nguyen, Kevin T Beier, Nikolai Hörmann, Wei-Cheng Chang, Zhe Zhang, Johnny Phong Do, Shenqin Yao, Michael J Krashes, Bosiljka Tasic, Ali Cetin, Hongkui Zeng, Zachary A Knight, Liqun Luo, Yang Dan
In humans and other mammalian species, lesions in the preoptic area of the hypothalamus cause profound sleep impairment, indicating a crucial role of the preoptic area in sleep generation. However, the underlying circuit mechanism remains poorly understood. Electrophysiological recordings and c-Fos immunohistochemistry have shown the existence of sleep-active neurons in the preoptic area, especially in the ventrolateral preoptic area and median preoptic nucleus. Pharmacogenetic activation of c-Fos-labelled sleep-active neurons has been shown to induce sleep...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28514170/discovery-of-novel-11-triazole-substituted-benzofuro-3-2-b-quinolone-derivatives-as-c-myc-g-quadruplex-specific-stabilizers-via-click-chemistry
#20
De-Ying Zeng, Guo-Tao Kuang, Shi-Ke Wang, Wang Peng, Shu-Ling Lin, Qi Zhang, Xiao-Xuan Su, Ming-Hao Hu, Honggen Wang, Jia-Heng Tan, Zhi-Shu Huang, Lian-Quan Gu, Tian-Miao Ou
The specificity of nucleic acids' binders is crucial for developing this kind of drugs, especially for novel G-quadruplexes' binders. Quindoline derivatives have been developed as G-quadruplex stabilizers with good interactive activities. In order to improve the selectivity and binding affinity of quindoline derivatives as c-myc G-quadruplex binding ligands, novel triazole containing benzofuroquinoline derivatives (T-BFQs) were designed and synthesized by using the 1,3-dipolar cycloaddition of a series of alkyne and azide building blocks...
May 17, 2017: Journal of Medicinal Chemistry
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