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epitope spreading

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https://www.readbyqxmd.com/read/28978707/prior-dengue-virus-exposure-shapes-t-cell-immunity-to-zika-virus-in-humans
#1
Alba Grifoni, John Pham, John Sidney, Patrick H O'Rourke, Sinu Paul, Bjoern Peters, Sheridan R Martini, Aruna D de Silva, Michael J Ricciardi, Diogo M Magnani, Cassia G T Silveira, Alvino Maestri, Priscilla R Costa, Luzia Maria de-Oliveira-Pinto, Elzinandes Leal de Azeredo, Paulo Vieira Damasco, Elizabeth Phillips, Simon Mallal, Aravinda M de Silva, Matthew Collins, Anna Durbin, Sean A Diehl, Cristhiam Cerpas, Angel Balmaseda, Guillermina Kuan, Josefina Coloma, Eva Harris, James E Crowe, Mars Stone, Phillip J Norris, Michael Busch, Hector Vivanco-Cid, Josephine Cox, Barney S Graham, Julie E Ledgerwood, Lance Turtle, Tom Solomon, Esper G Kallas, David I Watkins, Daniela Weiskopf, Alessandro Sette
While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether pre-existing dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with Tetravalent Dengue Attenuated Vaccines (TDLAV) recognize ZIKV-derived peptides...
October 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28947651/the-capsular-polysaccharide-of-acinetobacter-baumannii-is-an-obstacle-for-therapeutic-passive-immunization-strategies
#2
Shun Xin Wang-Lin, Ruth Olson, Janet M Beanan, Ulrike MacDonald, Joseph P Balthasar, Thomas A Russo
Acinetobacter baumannii has become an important concern to human health due to rapid development and wide spread of antimicrobial-resistant strains and high mortality associated with the infection. Passive immunizations with antisera targeting outer membrane proteins (OMPs) have shown encouraging results in protecting mice from A. baumannii infection; but monoclonal anti-OMP antibodies have not been developed and their potential therapeutic properties have not been explored. The goal of this report is to evaluate the antibacterial activity of monoclonal antibodies (mAbs) targeting outer membrane protein A (OmpA) of A...
September 25, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28940785/transglutaminases-in-autoimmune-and-inherited-skin-diseases-the-phenomena-of-epitope-spreading-and-functional-compensation
#3
REVIEW
Sarolta Kárpáti, Miklós Sárdy, Krisztián Németh, Balázs Mayer, Neil Smyth, Mats Paulsson, Heiko Traupe
Transglutaminases (TGs) are structurally and functionally related enzymes that modify the posttranslational structure and activity of proteins or peptides, and thus are able to turn on or switch off their function. Depending on location and activities, TGs are able to modify the signaling, the function and the fate of cells and extracellular connective tissues. Beside mouse models also human diseases enable us to appreciate the function of various TGs. In this paper skin diseases induced by genetic damages or autoimmune targeting of these enzymes will be discussed...
September 23, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28939757/pd-1-blockade-promotes-epitope-spreading-in-anticancer-cd8-t-cell-responses-by-preventing-fratricidal-death-of-subdominant-clones-to-relieve-immunodomination
#4
Arash Memarnejadian, Courtney E Meilleur, Christopher R Shaler, Khashayarsha Khazaie, Jack R Bennink, Todd D Schell, S M Mansour Haeryfar
The interactions between programmed death-1 (PD-1) and its ligands hamper tumor-specific CD8(+) T cell (TCD8) responses, and PD-1-based "checkpoint inhibitors" have shown promise in certain cancers, thus revitalizing interest in immunotherapy. PD-1-targeted therapies reverse TCD8 exhaustion/anergy. However, whether they alter the epitope breadth of TCD8 responses remains unclear. This is an important question because subdominant TCD8 are more likely than immunodominant clones to escape tolerance mechanisms and may contribute to protective anticancer immunity...
September 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28938005/recombinant-vaccines-of-a-cd4-t-cell-epitope-promote-efficient-control-of-paracoccidioides-brasiliensis-burden-by-restraining-primary-organ-infection
#5
Rodrigo Assunção Holanda, Julián Esteban Muñoz, Lucas Santos Dias, Leandro Buffoni Roque Silva, Julliana Ribeiro Alves Santos, Sthefany Pagliari, Érica Leandro Marciano Vieira, Tatiane Alves Paixão, Carlos Pelleschi Taborda, Daniel Assis Santos, Oscar Bruña-Romero
Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the thermally dimorphic fungi Paracoccidioides. Currently, there is no effective human vaccine that can be used in prophylactic or therapeutic regimes. We tested the hypothesis that the immunogenicity of the immunodominant CD4+ T-cell epitope (P10) of Paracoccidioides brasiliensis gp43 antigen might be significantly enhanced by using a hepatitis B virus-derived particle (VLP) as an antigen carrier. This chimera was administered to mice as a (His)6-purified protein (rPbT) or a replication-deficient human type 5 adenoviral vector (rAdPbT) in an immunoprophylaxis assay...
September 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28923084/viral-based-vaccine-tg4010-induces-broadening-of-specific-immune-response-and-improves-outcome-in-advanced-nsclc
#6
Caroline Tosch, Bérangère Bastien, Luc Barraud, Benoit Grellier, Virginie Nourtier, Murielle Gantzer, Jean Marc Limacher, Eric Quemeneur, Kaïdre Bendjama, Xavier Préville
BACKGROUND: Advanced non-small cell lung cancer patients receiving TG4010, a therapeutic viral vaccine encoding human Mucin 1 and interleukin-2 in addition to standard chemotherapy, displayed longer overall survival in comparison to that of patients treated with standard chemotherapy alone. Our study intended to establish the association between overall survival and vaccine-induced T cell responses against tumor associated antigens (TAA) targeted by the vaccine. METHOD: The TIME trial was a placebo-controlled, randomized phase II study aimed at assessing efficacy of TG4010 with chemotherapy in NSCLC...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28917306/evaluation-of-surface-antigen-tf1-17-in-feline-tritrichomonas-foetus-isolates
#7
E N Gould, L B Corbeil, S A Kania, M K Tolbert
Tritrichomonas foetus (T. foetus) is a flagellated protozoa that infects the distal ileum and proximal colon of domestic cats, as well as the urogenital tract of cattle. Feline trichomonosis is recognized as a prevalent cause of chronic diarrhea in cats worldwide. The suspected route of transmission is fecal-oral, with cats in densely crowded environments at highest risk for infection. Thus, the recommended strategy for minimizing spread of infection is to identify and isolate T. foetus-positive cats from the general population...
September 15, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28912784/comparison-of-the-protective-efficacy-of-neutralizing-epitopes-of-2009-pandemic-h1n1-influenza-hemagglutinin
#8
Bo Peng, Na Peng, Yanan Zhang, Fenghua Zhang, Xuguang Li, Haiyan Chang, Fang Fang, Fuyan Wang, Fangguo Lu, Ze Chen
The 2009 H1N1 influenza (Pdm09) pandemic has been referred to as the first influenza pandemic of the twenty-first century. There is a marked difference in antigenicity between the pandemic H1N1 virus and past seasonal H1N1 viruses, which allowed the pandemic virus to spread rapidly in humans. Antibodies (Abs) against hemagglutinin (HA), especially neutralizing Abs against epitopes in the head of HA, play critical roles in defending the host against the virus. Some preexisting neutralizing Abs that recognize neutralizing epitopes of Pdm09 HA, thereby affording cross-protection, have been reported...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28904948/recent-progress-in-deciphering-the-etiopathogenesis-of-primary-membranous-nephropathy
#9
REVIEW
Andreas Kronbichler, Jun Oh, Björn Meijers, Gert Mayer, Jae Il Shin
Primary membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. Discovery of several antibodies has contributed to an increased understanding of MN. Antibodies against the M-type phospholipase A2 receptor (PLA2R) are present in 50-100% with primary MN and are associated with a lower frequency of spontaneous remission. High levels are linked with a higher probability of treatment resistance, higher proteinuria, and impaired renal function, as well as a more rapid decline of kidney function during follow-up...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28883824/natural-killer-nk-cell-education-differentially-influences-hiv-antibody-dependent-nk-cell-activation-and-antibody-dependent-cellular-cytotoxicity
#10
REVIEW
Nicole F Bernard, Zahra Kiani, Alexandra Tremblay-McLean, Sanket A Kant, Christopher E Leeks, Franck P Dupuy
Immunotherapy using broadly neutralizing antibodies (bNAbs) endowed with Fc-mediated effector functions has been shown to be critical for protecting or controlling viral replication in animal models. In human, the RV144 Thai trial was the first trial to demonstrate a significant protection against HIV infection following vaccination. Analysis of the correlates of immune protection in this trial identified an association between the presence of antibody-dependent cellular cytotoxicity (ADCC) mediated by immunoglobulin G (IgG) antibodies (Abs) to HIV envelope (Env) V1/V2 loop structures and protection from infection, provided IgA Abs with competing specificity were not present...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28882619/variable-domain-glycosylation-of-acpa-igg-a-missing-link-in-the-maturation-of-the-acpa-response
#11
Ayla C Kempers, Lise Hafkenscheid, Hans Ulrich Scherer, René E M Toes
Anti-citrullinated Protein Antibodies (ACPA) are excellent markers for Rheumatoid arthritis (RA) and are postulated to have a pathogenic role in the disease process. A multistep model for the evolution of the ACPA response in RA was proposed in which an initial break of tolerance causes, as "first hit", "silent" production of ACPA without any clinical symptoms. The model further proposes that the ACPA immune response matures upon a certain (unknown) trigger, a "second hit", which leads to epitope spreading, an increase in ACPA titres and extended isotype usage before clinical RA manifestations...
September 4, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28841417/clonal-evolution-of-autoreactive-germinal-centers
#12
Søren E Degn, Cees E van der Poel, Daniel J Firl, Burcu Ayoglu, Fahd A Al Qureshah, Goran Bajic, Luka Mesin, Claude-Agnès Reynaud, Jean-Claude Weill, Paul J Utz, Gabriel D Victora, Michael C Carroll
Germinal centers (GCs) are the primary sites of clonal B cell expansion and affinity maturation, directing the production of high-affinity antibodies. This response is a central driver of pathogenesis in autoimmune diseases, such as systemic lupus erythematosus (SLE), but the natural history of autoreactive GCs remains unclear. Here, we present a novel mouse model where the presence of a single autoreactive B cell clone drives the TLR7-dependent activation, expansion, and differentiation of other autoreactive B cells in spontaneous GCs...
August 24, 2017: Cell
https://www.readbyqxmd.com/read/28807856/low-levels-of-genetic-diversity-associated-with-evidence-of-negative-selection-on-the-babesia-bovis-apical-membrane-antigen-1-from-parasite-populations-in-thailand
#13
Amarin Rittipornlertrak, Boondarika Nambooppha, Pacharathon Simking, Veerasak Punyapornwithaya, Saruda Tiwananthagorn, Sathaporn Jittapalapong, Yang-Tsung Chung, Nattawooti Sthitmatee
Babesia bovis, a parasite infecting cattle and buffalo, continues to spread throughout the developing world. The babesial vaccine was developed to be a sustainable alternative treatment to control the parasite. However, genetic diversity is a major obstacle for designing and developing a safe and effective vaccine. The apical membrane antigen 1 (AMA-1) is considered to be a potential vaccine candidate antigen among immunogenic genes of B. bovis. To gain a more comprehensive understanding of B. bovis AMA-1 (BbAMA-1), three B...
August 12, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28805676/inhibitors-of-deubiquitinating-enzymes-block-hiv-1-replication-and-augment-the-presentation-of-gag-derived-mhc-i-epitopes
#14
Christian Setz, Melanie Friedrich, Pia Rauch, Kirsten Fraedrich, Alina Matthaei, Maximilian Traxdorf, Ulrich Schubert
In recent years it has been well established that two major constituent parts of the ubiquitin proteasome system (UPS)-the proteasome holoenzymes and a number of ubiquitin ligases-play a crucial role, not only in virus replication but also in the regulation of the immunogenicity of human immunodeficiency virus type 1 (HIV-1). However, the role in HIV-1 replication of the third major component, the deubiquitinating enzymes (DUBs), has remained largely unknown. In this study, we show that the DUB-inhibitors (DIs) P22077 and PR-619, specific for the DUBs USP7 and USP47, impair Gag processing and thereby reduce the infectivity of released virions without affecting viral protease activity...
August 12, 2017: Viruses
https://www.readbyqxmd.com/read/28758349/appearance-of-us-like-porcine-epidemic-diarrhoea-virus-pedv-strains-before-us-outbreaks-and-genetic-heterogeneity-of-pedvs-collected-in-northern-vietnam-during-2012-2015
#15
N V Diep, M Sueyoshi, U Izzati, N Fuke, A P P Teh, N T Lan, R Yamaguchi
Porcine epidemic diarrhoea virus (PEDV) is the aetiologic agent of porcine epidemic diarrhoea (PED), a highly contagious enteric disease that is threatening the swine industry globally. Since PED was first reported in Southern Vietnam in 2009, the disease has spread throughout the country and caused substantial economic losses. To identify PEDVs responsible for the recent outbreaks, the full-length spike (S) gene of 25 field PEDV strains collected from seven northern provinces of Vietnam was sequenced and analysed...
July 30, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/28756229/role-of-the-extracellular-matrix-located-mac-2-binding-protein-as-an-interactor-of-the-wnt-proteins
#16
Timo Pikkarainen, Tuomas Nurmi, Takako Sasaki, Ulrich Bergmann, Seppo Vainio
The Wnt proteins constitute a conserved family of secreted palmitoleate-containing signaling proteins that play important roles in development and tissue homeostasis. Their hydrophobic nature has raised the question of how the proteins are transported outside the cells. Accumulating evidence suggests that several different mechanisms, including transport by lipoprotein particles and exosomes, may contribute to this process. Here, we expressed epitope-tagged Wnt4 in HEK293 cells, and identified Mac-2 binding protein (Mac-2BP) as its binding partner in the serum-free conditioned medium...
September 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28740150/identification-of-putative-unique-immunogenic-zikv-and-denv1-4-peptides-for-diagnostic-cellular-based-tests
#17
Aaron L Oom, Davey Smith, Kevan Akrami
Since the re-emergence of Zika virus in 2014 and subsequent association with microcephaly, much work has focused on the development of a vaccine to halt its spread throughout the world. The mosquito vector that transmits this virus is widespread and responsible for the spread of other arboviridae including Dengue. Current diagnostic methods rely on serologic testing that are complicated by cross reactivity and therefore unable to distinguish Zika from Dengue infection in the absence of virus isolation. We performed an in silico analysis to identify potential epitopes that may stimulate a unique T-lymphocyte response to distinguish prior infection with Zika or Dengue...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729867/exposure-to-the-epstein-barr-viral-antigen-latent-membrane-protein-1-induces-myelin-reactive-antibodies-in-vivo
#18
Yakov Lomakin, Georgii Pavlovich Arapidi, Alexander Chernov, Rustam Ziganshin, Evgenii Tcyganov, Irina Lyadova, Ivan Olegovich Butenko, Maria Osetrova, Natalia Ponomarenko, Georgy Telegin, Vadim Markovich Govorun, Alexander Gabibov, Alexey Belogurov
Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease of the central nervous system (CNS). Cross-reactivity of neuronal proteins with exogenous antigens is considered one of the possible mechanisms of MS triggering. Previously, we showed that monoclonal myelin basic protein (MBP)-specific antibodies from MS patients cross-react with Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1). In this study, we report that exposure of mice to LMP1 results in induction of myelin-reactive autoantibodies in vivo...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28680713/robust-immunoreactivity-of-teenager-sera-against-peptide-19-from-porphyromonas-gingivalis-hsp60
#19
Eun-Young Kwon, Gil Sun Cha, Ji-Young Joo, Ju-Youn Lee, Jeomil Choi
PURPOSE: Epitope spreading is a phenomenon in which distinct subdominant epitopes become major targets of the immune response. Heat shock protein (HSP) 60 from Porphyromonas gingivalis (PgHSP60) and peptide 19 from PgHSP60 (Pep19) are immunodominant epitopes in autoimmune disease patients, including those with periodontitis. It remains unclear whether Pep19 is a dominant epitope in subjects without periodontitis or autoimmune disease. The purpose of this study was to determine the epitope spreading pattern and verify Pep19 as an immunodominant epitope in healthy teenagers using dot immunoblot analysis...
June 2017: Journal of Periodontal & Implant Science
https://www.readbyqxmd.com/read/28680335/analysis-of-the-autoimmune-response-against-bp180-and-bp230-in-ethnic-poles-with-neurodegenerative-disorders-and-bullous-pemphigoid
#20
Justyna Gornowicz-Porowska, Agnieszka Seraszek-Jaros, Monika Bowszyc-Dmochowska, Elżbieta Kaczmarek, Paweł Pietkiewicz, Paweł Bartkiewicz, Marian Dmochowski
Recent studies postulated the association between bullous pemphigoid (BP) and neurodegenerative disorders (ND). The autoantibodies to BP180 and/or BP230 may be present not only in BP, but also in ND as neuronal isoforms of these proteins are identified in the central nervous system. However, there are only scant data about the precise pathogenetic mechanisms interlinking ND and BP as well as the immunologic profile in these patients. The aim is to analyze the serological immunopathological profiles (anti-BP180 IgG, anti-BP230 IgG) in BP patients with and without ND in order to identify the specific autoantibody(ies) and corresponding antigens responsible for ND development in BP patients...
2017: Central-European Journal of Immunology
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