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T cell specificity

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https://www.readbyqxmd.com/read/29168728/interference-of-htlv-1-tax-protein-with-cell-polarity-regulators-defining-the-subcellular-localization-of-the-tax-dlg1-interaction
#1
Federico Marziali, Marina Bugnon Valdano, Clarisse Brunet Avalos, Lucía Moriena, Ana Laura Cavatorta, Daniela Gardiol
Human T cell leukemia virus (HTLV)-1 Tax (Tax) protein is very important in viral replication and cell transformation. Tax localizes in the nucleus and cytoplasm in association with organelles. Some activities of Tax depend on interactions with PDZ (PSD-95/Discs Large/Z0-1) domain-containing proteins such as Discs large protein 1 (DLG1) which is involved in cell polarity and proliferation. The DLG1 interaction results in a cytoplasmic co-localization pattern resembling vesicular aggregates, the nature of which is still unknown...
November 23, 2017: Viruses
https://www.readbyqxmd.com/read/29168504/mechanism-of-tandem-duplication-formation-in-brca1-mutant-cells
#2
Nicholas A Willis, Richard L Frock, Francesca Menghi, Erin E Duffey, Arvind Panday, Virginia Camacho, E Paul Hasty, Edison T Liu, Frederick W Alt, Ralph Scully
Small, approximately 10-kilobase microhomology-mediated tandem duplications are abundant in the genomes of BRCA1-linked but not BRCA2-linked breast cancer. Here we define the mechanism underlying this rearrangement signature. We show that, in primary mammalian cells, BRCA1, but not BRCA2, suppresses the formation of tandem duplications at a site-specific chromosomal replication fork barrier imposed by the binding of Tus proteins to an array of Ter sites. BRCA1 has no equivalent role at chromosomal double-stranded DNA breaks, indicating that tandem duplications form specifically at stalled forks...
November 22, 2017: Nature
https://www.readbyqxmd.com/read/29168424/a-prognostic-scoring-system-using-inflammatory-response-biomarkers-in-oral-cavity-squamous-cell-carcinoma-patients-who-underwent-surgery-based-treatment
#3
Young Min Park, Kyung Ho Oh, Jae-Gu Cho, Seung-Kuk Baek, Soon-Young Kwon, Kwang-Yoon Jung, Jeong-Soo Woo
BACKGROUND: The aim of this study was to evaluate the effectiveness of a scoring system based on the lymphocyte-to-monocyte ratio, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio for predicting disease-specific survival of oral cancer patients treated by surgery. METHODS: From January 2007 to December 2016, we retrospectively analyzed data from 69 oral cancer patients who received surgery. RESULTS: Lymphocyte-to-monocyte ratio was significantly associated with T classification, N classification, and pathologic stage...
November 23, 2017: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/29168191/genetic-variants-in-il15-promoter-affect-transcription-activity-and-intramuscular-fat-deposition-in-longissimus-dorsi-muscle-of-pigs
#4
D He, Z Jiang, Y Tian, H Han, M Xia, W Wei, L Zhang, J Chen
Intramuscular fat (IMF) content is a key aspect of pork quality. Elucidation of intramuscular adipocyte regulation mechanisms is important for improving IMF content. Intramuscular adipocytes are dispersed among muscle fibers, so they are inclined to be affected by muscle-derived factors. Interleukin-15 is a major muscle-secreted factor. In this study, the genetic and physiological impacts of IL15 on adipogenesis is investigated. The promoter region of IL15 was scanned by comparative sequencing using two DNA pools of high- and low-IMF individuals...
November 22, 2017: Animal Genetics
https://www.readbyqxmd.com/read/29168073/fungus-specific-cd4-t-cells-as-specific-sensors-for-identification-of-pulmonary-fungal-infections
#5
Alexander Scheffold, Carsten Schwarz, Petra Bacher
Patients with cystic fibrosis (CF) suffer from chronic lung infections, caused by bacterial, viral or fungal pathogens, which determine morbidity and mortality. The contribution of individual pathogens to chronic disease and acute lung exacerbations is often difficult to determine due to the complex composition of the lung microbiome in CF. In particular, the relevance of fungal pathogens in CF airways remains poorly understood due to limitations of current diagnostics to identify the presence of fungal pathogens and to resolve the individual host-pathogen interaction status...
November 22, 2017: Mycopathologia
https://www.readbyqxmd.com/read/29167844/recellularization-of-decellularized-adipose-tissue-derived-stem-cells-role-of-the-cell-secreted-extracellular-matrix-in-cellular-differentiation
#6
V Guneta, Z Zhou, N S Tan, S Sugii, M T C Wong, C Choong
Adipose-derived stem cells (ASCs) are found in a location within the adipose tissue known as the stem cell niche. The ASCs in the niche are maintained in the quiescent state, and upon exposure to various microenvironmental triggers are prompted to undergo proliferation or differentiation. These microenvironmental triggers also modulate the extracellular matrix (ECM), which interacts with the cells through the cytoskeleton and induces downstream events inside the cells that bring about a change in cell behaviour...
November 23, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/29167820/engineering-chimeric-antigen-receptor-t-cells-to-treat-glioblastoma
#7
Bryan D Choi, Donald M O'Rourke, Marcela V Maus
Immunotherapy has emerged as a promising strategy for glioblastoma (GBM), a disease that remains universally fatal despite currently available standard-of-care. Adoptive T cell therapy has been shown to produce potent antitumor immunity while obviating the need for traditional antigen presentation and primary immune responses. Chimeric antigen receptors (CARs) are specialized molecules that can be expressed on the surface of T cells allowing for redirected cytotoxicity against tumor antigens of interest. To date, the application of CAR T cells for GBM has been relatively limited, in large part due to a dearth of well-described tumor specific antigens that are both homogenously and frequently expressed...
August 2017: J Target Ther Cancer
https://www.readbyqxmd.com/read/29167800/cross-species-complementation-of-bacterial-and-eukaryotic-type-cardiolipin-synthases
#8
Petra Gottier, Mauro Serricchio, Rita Vitale, Angela Corcelli, Peter Bütikofer
The glycerophospholipid cardiolipin is a unique constituent of bacterial and mitochondrial membranes. It is involved in forming and stabilizing high molecular mass membrane protein complexes and in maintaining membrane architecture. Absence of cardiolipin leads to reduced efficiency of the electron transport chain, decreased membrane potential, and, ultimately, impaired respiratory metabolism. For the protozoan parasite Trypanosoma brucei cardiolipin synthesis is essential for survival, indicating that the enzymes involved in cardiolipin production represent potential drug targets...
November 3, 2017: Microbial Cell
https://www.readbyqxmd.com/read/29167673/inhibition-of-allograft-inflammatory-factor-1-in-dendritic-cells-restrains-cd4-t-cell-effector-responses-and-induces-cd25-foxp3-t-regulatory-subsets
#9
Diana M Elizondo, Temesgen E Andargie, Dazhi Yang, Apollo D Kacsinta, Michael W Lipscomb
Allograft inflammatory factor-1 (AIF1) is a cytoplasmic scaffold protein shown to influence immune responses in macrophages and microglial cells. The protein contains Ca(2+) binding EF-hand and PDZ interaction domains important for mediating intracellular signaling complexes. This study now reports that AIF1 is expressed in CD11c(+) dendritic cells (DC) and silencing of expression restrains induction of antigen-specific CD4(+) T cell effector responses. AIF1 knockdown in murine DC resulted in impaired T cell proliferation and skewed polarization away from T helper type 1 and 17 fates...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29167489/t-helper-cells-with-specificity-for-an-antigen-in-cardiomyocytes-promote-pressure-overload-induced-progression-from-hypertrophy-to-heart-failure
#10
Carina Gröschel, André Sasse, Charlotte Röhrborn, Sebastian Monecke, Michael Didié, Leslie Elsner, Vanessa Kruse, Gertrude Bunt, Andrew H Lichtman, Karl Toischer, Wolfram-Hubertus Zimmermann, Gerd Hasenfuß, Ralf Dressel
We investigated whether CD4(+)-T cells with specificity for an antigen in cardiomyocytes promote the progression from hypertrophy to heart failure in mice with increased pressure load due to transverse aortic constriction (TAC). OT-II mice expressing a transgenic T cell receptor (TCR) with specificity for ovalbumin (OVA) on CD4(+)-T cells and cMy-mOVA mice expressing OVA on cardiomyocytes were crossed. The resulting cMy-mOVA-OT-II mice did not display signs of spontaneous autoimmunity despite the fact that their OVA-specific CD4(+)-T cells were not anergic...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29167392/tcr-engagement-negatively-affects-cd8-but-not-cd4-car-t-cell-expansion-and-leukemic-clearance
#11
Yinmeng Yang, M Eric Kohler, Christopher D Chien, Christopher T Sauter, Elad Jacoby, Chunhua Yan, Ying Hu, Kelsey Wanhainen, Haiying Qin, Terry J Fry
Chimeric antigen receptor (CAR)-expressing T cells induce durable remissions in patients with relapsed/refractory B cell malignancies. CARs are synthetic constructs that, when introduced into mature T cells, confer a second, non-major histocompatibility complex-restricted specificity in addition to the endogenous T cell receptor (TCR). The implications of TCR activation on CAR T cell efficacy has not been well defined. Using an immunocompetent, syngeneic murine model of CD19-targeted CAR T cell therapy for pre-B cell acute lymphoblastic leukemia in which the CAR is introduced into T cells with known TCR specificity, we demonstrate loss of CD8 CAR T cell efficacy associated with T cell exhaustion and apoptosis when TCR antigen is present...
November 22, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29167337/differential-immunodominance-hierarchy-of-cd8-t-cell-responses-in-hla-b-27-05-and-b-27-02-mediated-control-of-hiv-1-infection
#12
Emily Adland, Matilda Hill, Nora Lavandier, Anna Csala, Anne Edwards, Fabian Chen, Marek Radkowski, Justyna D Kowalska, Dimitrios Paraskevis, Angelos Hatzakis, Humberto Valenzuela-Ponce, Katja Pfafferott, Ian Williams, Pierre Pellegrino, Persephone Borrow, Masahiko Mori, Jürgen Rockstroh, Julia G Prado, Beatriz Mothe, Judith Dalmau, Javier Martinez-Picado, Gareth Tudor-Williams, John Frater, Anette Stryhn, Soren Buus, Gustavo Reyes Teran, Simon Mallal, Mina John, Susan Buchbinder, Gregory Kirk, Jeffrey Martin, Nelson Michael, Jacques Fellay, Steve Deeks, Bruce Walker, Santiago Avila-Rios, David Cole, Christian Brander, Mary Carrington, Philip Goulder
The well-characterised association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8+ T-cell responses towards the conserved Gag 263-272 ('KK10') and Pol 901-909 'KY9' epitopes. We here studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely-related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 associate with slower disease progression and lower viral loads...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29167333/authentic-patient-derived-hepatitis-c-virus-infects-and-productively-replicates-in-primary-cd4-and-cd8-t-lymphocytes-in-vitro
#13
Georgia Skardasi, Annie Y Chen, Tomasz I Michalak
Accumulated evidence indicates that immune cells can support replication of hepatitis C virus (HCV) in infected patients and in culture. However, there is a scarcity of data on the degree to which individual immune cell types support HCV propagation and on characteristics of virus assembled. We investigated the ability of authentic, patient-derived HCV to infect in vitro two closely related but functionally distinct immune cell types, CD4+ and CD8+ T lymphocytes, and assessed properties of virus produced by these cells...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29167316/quantitative-phosphoproteomic-analysis-reveals-shared-and-specific-targets-of-arabidopsis-mpk3-mpk4-and-mpk6
#14
Naganand Rayapuram, Jean Bigeard, Hanna Alhoraibi, Ludovic Bonhomme, Anne-Marie Hesse, Joelle Vinh, Heribert Hirt, Delphine Pflieger
In Arabidopsis, mitogen-activated protein kinases MPK3, MPK4 and MPK6 constitute essential relays for a variety of functions including cell division, development and innate immunity. While some substrates of MPK3, MPK4 and MPK6 have been identified, the picture is still far from complete. To identify substrates of these MAPKs likely involved in cell division, growth and development we compared the phosphoproteomes of wild-type and mpk3, mpk4 and mpk6. To study the function of these MAPKs in innate immunity, we analyzed their phosphoproteomes following microbe-associated molecular pattern (MAMP) treatment...
November 22, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29167311/the-human-ctf4-orthologue-and-1-interacts-with-dna-polymerase-%C3%AE-primase-via-its-unique-c-terminal-hmg-box
#15
Mairi L Kilkenny, Aline C Simon, Jack Mainwaring, David Wirthensohn, Sandro Holzer, Luca Pellegrini
A dynamic multi-protein assembly known as the replisome is responsible for DNA synthesis in eukaryotic cells. In yeast, the hub protein Ctf4 bridges DNA helicase and DNA polymerase and recruits factors with roles in metabolic processes coupled to DNA replication. An important question in DNA replication is the extent to which the molecular architecture of the replisome is conserved between yeast and higher eukaryotes. Here, we describe the biochemical basis for the interaction of the human CTF4-orthologue AND-1 with DNA polymerase α (Pol α)/primase, the replicative polymerase that initiates DNA synthesis...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29167234/route-of-antigen-presentation-can-determine-the-selection-of-foxp3-dependent-or-foxp3-independent-dominant-immune-tolerance
#16
Ana Agua-Doce, Marta Caridade, Vanessa G Oliveira, Lisa Bergman, Maria C Lafaille, Juan J Lafaille, Jocelyne Demengeot, Luis Graca
It has been shown that dominant tolerance, namely in transplantation, requires Foxp3(+) regulatory T cells. Although most tolerance-inducing regimens rely on regulatory T cells, we found that induction of tolerance to proteins in aluminum hydroxide can be achieved in Foxp3-deficient mice using nondepleting anti-CD4 Abs. This type of tolerance is Ag specific, and tolerant mice retain immune competence to respond to unrelated Ags. We demonstrated with chicken OVA-specific TCR-transgenic mice that the same tolerizing protocol (CD4 blockade) and the same target Ag (OVA) achieves Foxp3-dependent transplantation tolerance to OVA-expressing skin grafts, but Foxp3-independent tolerance when the Ag is provided as OVA-aluminum hydroxide...
November 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29167197/rare-pfcsp-c-terminal-antibodies-induced-by-live-sporozoite-vaccination-are-ineffective-against-malaria-infection
#17
Stephen W Scally, Rajagopal Murugan, Alexandre Bosch, Gianna Triller, Giulia Costa, Benjamin Mordmüller, Peter G Kremsner, B Kim Lee Sim, Stephen L Hoffman, Elena A Levashina, Hedda Wardemann, Jean-Philippe Julien
Antibodies against the central repeat of the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) inhibit parasite activity and correlate with protection from malaria. However, the humoral response to the PfCSP C terminus (C-PfCSP) is less well characterized. Here, we describe B cell responses to C-PfCSP from European donors who underwent immunization with live Pf sporozoites (PfSPZ Challenge) under chloroquine prophylaxis (PfSPZ-CVac), and were protected against controlled human malaria infection. Out of 215 PfCSP-reactive monoclonal antibodies, only two unique antibodies were specific for C-PfCSP, highlighting the rare occurrence of C-PfCSP-reactive B cells in PfSPZ-CVac-induced protective immunity...
November 22, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29166735/-the-specific-cytotoxicities-of-chimeric-antigen-receptor-engineered-t-cells-on-different-lymphomas
#18
R Zhang, Q Deng, S N Sui, X Jin, M F Zhao
Objective: To investigate the specific cytotoxicities of the second and third generations of chimeric antigen receptor (CAR) -engineered T cells (CAR-T) on different lymphomas. Methods: CAR-Ts were prepared by lentivirus packaging and infection of T cells. CCK-8, ELISA and Lactate dehydrogenase cytotoxicity assay were applied to detect the proliferation capacity, the secretion level of inflammatory factor and the specific cytotoxicity. Flow cytometry assay showed the specific cytotoxicity and residual level of CAR-T in lymphomas of treated mice...
October 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29166711/-effects-of-caspase-1-inhibitor-vx765-on-cold-restraint-stress-induced-acute-gastric-ulcer-in-mice
#19
S Q Zheng, X D Hong, T S Chen, P F Luo, S C Xiao
Objective: To investigate the protective effects of caspase-1 inhibitor VX765 on gastric mucosa of mice with cold-restraint stress-induced acute gastric ulcer. Methods: Twenty-four specific pathogen free male C57BL/6J mice were divided into normal control group (NC), cold restrain group (CR), VX765 pre-treatment+ cold restrain group (VCR), and rabeprazole pre-treatment+ cold restrain group (RCR) according to the random number table, with 6 mice in each group. Mice in group NC were injected intraperitoneally with solution of 10 mL/kg dimethylsulfoxide (DMSO) and phosphate buffer solution (PBS)...
November 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/29166616/the-aryl-hydrocarbon-receptor-preferentially-marks-and-promotes-gut-regulatory-t-cells
#20
Jian Ye, Ju Qiu, John W Bostick, Aki Ueda, Hilde Schjerven, Shiyang Li, Christian Jobin, Zong-Ming E Chen, Liang Zhou
The local environment may affect the development and function of tissue-resident T regulatory cells (Tregs), which are crucial for controlling inflammation. Although the aryl hydrocarbon receptor (Ahr), an environmental sensor, is expressed by Tregs, its role in Treg cell development and/or function remains elusive. Here, we generated mouse genetic models to ablate or activate Ahr expression specifically in Tregs. We showed that Ahr was expressed more abundantly by peripherally induced Tregs (pTregs) in the gut and that its expression was independent of microbiota...
November 21, 2017: Cell Reports
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