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https://www.readbyqxmd.com/read/29343547/molecular-pathways-for-immune-recognition-of-preproinsulin-signal-peptide-in-type-1-diabetes
#1
Deborah Kronenberg-Versteeg, Martin Eichmann, Mark A Russell, Arnoud de Ru, Beate Hehn, Norkhairin Yusuf, Peter A van Veelen, Sarah J Richardson, Noel G Morgan, Marius K Lemberg, Mark Peakman
The signal peptide region of preproinsulin (PPI) contains epitopes targeted by human leucocyte antigen-A (HLA-A)-restricted (HLA-A0201, A2402) cytotoxic T-cells as part of the pathogenesis of β-cell destruction in type 1 diabetes. We extended PPI epitope discovery to disease-associated HLA-B*1801 and HLA-B*3906 (risk) and HLA-A*1101 and HLA-B*3801 (protective) alleles revealing that 4/6 alleles present epitopes derived from the signal peptide region. During co-translational translocation of PPI, its signal peptide is cleaved and retained within the endoplasmic reticulum (ER) membrane, implying it is processed for immune recognition outside of the canonical, proteasome-directed pathway...
January 17, 2018: Diabetes
https://www.readbyqxmd.com/read/29343295/cytotoxic-t-lymphocytes-from-cattle-sharing-the-same-mhc-class-i-haplotype-and-immunized-with-live-theileria-parva-sporozoites-differ-in-antigenic-specificity
#2
Lucilla Steinaa, Nicholas Svitek, Elias Awino, Rosemary Saya, Philip Toye
OBJECTIVES: The objective of this study was to assess whether cytotoxic T cells (CTL) generated by the live vaccine, known as "ITM Muguga cocktail", which is used for the cattle disease East Cost fever (ECF) in Sub-Saharan Africa, showed a broad reactivity against many different strains of the causative parasite Theileria parva. We also assessed whether immune responses were similar in cattle expressing the same MHC class I haplotypes. RESULTS: The antigenic specificity of CTL from MHC class I-matched cattle vaccinated with the Muguga cocktail were different...
January 17, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29340620/delivery-of-tapasin-modified-ctl-epitope-peptide-via-cytoplasmic-transduction-peptide-induces-ctls-by-jak-stat-signaling-pathway-in-vivo
#3
Shanshan Wu, Xiaohua Chen, Yuyan Tang, Yi Zhang, Dan Li, Jie Chen, Jieling Wang, Zhenghao Tang, Guoqing Zang, Yongsheng Yu
Hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) play a vital role in viral control and clearance. Recent studies have elucidated that Tapasin, an endoplasmic reticulum chaperone, is a well-known molecule that appears to be essential in peptide-loading process. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway plays an important role in immune response regulation and cytokines secretion. We have previously verified that fusion protein CTP-HBcAg18-27-Tapasin could facilitate the maturation of bone marrow derived dendritic cells and enhance specific CTLs responses in vitro, which might be associated with the activation of JAK/STAT signaling pathway...
January 11, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29338056/context-dependent-autoprocessing-of-human-immunodeficiency-virus-type-1-protease-precursors
#4
ChihFeng Tien, Liangqun Huang, Susan M Watanabe, Jordan T Speidel, Carol A Carter, Chaoping Chen
HIV-1 protease autoprocessing is responsible for liberation of free mature protease (PR) from the Gag-Pol polyprotein precursor. A cell-based model system was previously developed to examine the autoprocessing mechanism of fusion precursors carrying the p6*-PR miniprecursor sandwiched between various proteins or epitopes. We here report that precursor autoprocessing is context-dependent as its activity and outcomes can be modulated by sequences upstream of p6*-PR. This was exemplified by the 26aa maltose binding protein (MBP) signal peptide (SigP) when placed at the N-terminus of a fusion precursor...
2018: PloS One
https://www.readbyqxmd.com/read/29331515/mhc-class-i-loaded-ligands-from-breast-cancer-cell-lines-a-potential-hla-i-typed-antigen-collection
#5
Dmitri V Rozanov, Nikita D Rozanov, Kami Chiotti, Ashok Reddy, Phillip A Wilmarth, Larry L David, Seung W Cha, Sunghee Woo, Pavel Pevzner, Vineet Bafna, Gregory G Burrows, Juha K Rantala, Trevor Levin, Pavana Anur, Katie Johnson-Camacho, Shaadi Tabatabaei, Daniel J Munson, Tullia C Bruno, Jill E Slansky, John W Kappler, Naoto Hirano, Sebastian Boegel, Bernard A Fox, Colt Egelston, Diana L Simons, Grecia Jimenez, Peter P Lee, Joe W Gray, Paul T Spellman
To build a catalog of peptides presented by breast cancer cells, we undertook systematic MHC class I immunoprecipitation followed by elution of MHC class I-loaded peptides in breast cancer cells. We determined the sequence of 3196 MHC class I ligands representing 1921 proteins from a panel of 20 breast cancer cell lines. After removing duplicate peptides, i.e., the same peptide eluted from more than one cell line, the total number of unique peptides was 2740. Of the unique peptides eluted, more than 1750 had been previously identified, and of these, sixteen have been shown to be immunogenic...
January 10, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29330423/t-cell-immunity-to-zika-virus-targets-immunodominant-epitopes-that-show-cross-reactivity-with-other-flaviviruses
#6
C J Reynolds, O M Suleyman, A M Ortega-Prieto, J K Skelton, P Bonnesoeur, A Blohm, V Carregaro, J S Silva, E A James, B Maillère, M Dorner, R J Boyton, D M Altmann
Zika virus (ZIKV) Infection has several outcomes from asymptomatic exposure to rash, conjunctivitis, Guillain-Barré syndrome or congenital Zika syndrome. Analysis of ZIKV immunity is confounded by the fact that several related Flaviviruses infect humans, including Dengue virus 1-4, West Nile virus and Yellow Fever virus. HLA class II restricted T cell cross-reactivity between ZIKV and other Flaviviruses infection(s) or vaccination may contribute to protection or to enhanced immunopathology. We mapped immunodominant, HLA class II restricted, CD4 epitopes from ZIKV Envelope (Env), and Non-structural (NS) NS1, NS3 and NS5 antigens in HLA class II transgenic mice...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330323/il-10-deficiency-reveals-a-role-for-tlr2-dependent-bystander-activation-of-t-cells-in-lyme-arthritis
#7
Sarah K Whiteside, Jeremy P Snook, Ying Ma, F Lynn Sonderegger, Colleen Fisher, Charisse Petersen, James F Zachary, June L Round, Matthew A Williams, Janis J Weis
T cells predominate the immune responses in the synovial fluid of patients with persistent Lyme arthritis; however, their role in Lyme disease remains poorly defined. Using a murine model of persistent Lyme arthritis, we observed that bystander activation of CD4+ and CD8+ T cells leads to arthritis-promoting IFN-γ, similar to the inflammatory environment seen in the synovial tissue of patients with posttreatment Lyme disease. TCR transgenic mice containing monoclonal specificity toward non-Borrelia epitopes confirmed that bystander T cell activation was responsible for disease development...
January 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29328998/immunization-of-mice-with-egg1y162-1-2-provides-protection-against-echinococcus-granulosus-infection-in-balb-c-mice
#8
Fengbo Zhang, Shaoyu Li, Yuejie Zhu, Chuntao Zhang, Yujiao Li, Haimei Ma, Nannan Pang, Mengting An, Hongying Wang, Jianbing Ding
AIMS: This study is to predict and purify the T-B combined epitopes of egG1Y162 antigen in Echinococcus granulosus, and to evaluate their immunogenicity in mice. METHODS: The bioinformatics software was used to predict the T-B combined epitopes of egG1Y162 antigen. Recombinant egG1Y161/2 peptides were constructed, expressed and purified. Mice were immunized with egG1Y161/2 peptides. The serum and spleen cells were isolated. The isolated spleen cells were stimulated with egG1Y161/2 peptides in vitro and the culture supernatant was collected...
January 9, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29323725/serum-igg-antibodies-from-healthy-subjects-up-to-100-years-old-react-to-jc-polyomavirus
#9
Ilaria Bononi, Elisa Mazzoni, Silvia Pietrobon, Marco Manfredini, Elena Trregiani, Marika Rossini, Francesca Lotito, Giovanni Guerra, Paola Rizzo, Fernanda Martini, Mauro Tognon
JC polyomavirus (JCPyV) was identified in 1971 in the brain tissue of a patient (J.C.) affected by the progressive multifocal leukoencephalopathy (PML). JCPyV encodes for the oncoproteins large T antigen (Tag) and small t-antigen (tag). These oncoproteins are responsible of the cell transformation and tumorigenesis in experimental animals. JCPyV is ubiquitous in human populations. After the primary infection, which is usually asymptomatic, JCPyV remains lifelong in the host in a latent phase. Its reactivation may occur in heathy subjects and immunocompromised patients...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29319889/epitope-targeted-macrocyclic-peptide-ligand-with-picomolar-cooperative-binding-to-interleukin-17f
#10
Bert T Lai, Jeré A Wilson, Jacquie Malette Loredo, Suresh M Pitram, Nicole A LaBerge, James R Heath, Heather Agnew
The IL-17 cytokine family is associated with multiple immune and autoimmune diseases and comprises important diagnostic and therapeutic targets. We developed epitope-targeted ligands designed for differential detection of human IL-17F and its closest homologue IL-17A. Non-overlapping and unique epitopes on IL-17F and IL-17A were identified by comparative sequence analysis of the two proteins. Synthetic variants of these epitopes were utilized as targets for in situ click screens against a comprehensive library of synthetic peptide macrocycles with 5-mer variable regions...
January 10, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29317703/modeling-tumor-immunity-of-mouse-glioblastoma-by-exhausted-cd8-t-cells
#11
Hiroshi Nakashima, Quazim A Alayo, Pablo Penaloza-MacMaster, Gordon J Freeman, Vijay K Kuchroo, David A Reardon, Soledad Fernandez, Michael Caligiuri, E Antonio Chiocca
T cell exhaustion occurs during chronic infection and cancers. Programmed cell death protein-1 (PD-1) is a major inhibitory checkpoint receptor involved in T cell exhaustion. Blocking antibodies (Abs) against PD-1 or its ligand, PD-L1, have been shown to reverse T cell exhaustion during chronic infection and cancers, leading to improved control of persistent antigen. However, modeling tumor-specific T cell responses in mouse has been difficult due to the lack of reagents to detect and phenotype tumor-specific immune responses...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316918/in-silico-epitope-mapping-and-experimental-evaluation-of-the-merozoite-adhesive-erythrocytic-binding-protein-maebl-as-a-malaria-vaccine-candidate
#12
Pedro Cravo, Renato B Machado, Juliana A Leite, Taizy Leda, Rossarin Suwanarusk, Najara Bittencourt, Letusa Albrecht, Carla Judice, Stefanie C P Lopes, Marcus V G Lacerda, Marcelo U Ferreira, Irene S Soares, Yun Shan Goh, Daniel Y Bargieri, François Nosten, Bruce Russell, Laurent Rénia, Fabio T M Costa
BACKGROUND: Technical limitations for culturing the human malaria parasite Plasmodium vivax have impaired the discovery of vaccine candidates, challenging the malaria eradication agenda. The immunogenicity of the M2 domain of the Merozoite Adhesive Erythrocytic Binding Protein (MAEBL) antigen cloned from the Plasmodium yoelii murine parasite, has been previously demonstrated. RESULTS: Detailed epitope mapping of MAEBL through immunoinformatics identified several MHCI, MHCII and B cell epitopes throughout the peptide, with several of these lying in the M2 domain and being conserved between P...
January 10, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29315598/improved-methods-for-predicting-peptide-binding-affinity-to-mhc-class-ii-molecules
#13
Kamilla Kjaergaard Jensen, Massimo Andreatta, Paolo Marcatili, Søren Buus, Jason A Greenbaum, Zhen Yan, Alessandro Sette, Bjoern Peters, Morten Nielsen
Major histocompatibility complex class II (MHC-II) molecules are expressed on the surface of professional antigen presenting cells where they display peptides to T helper cells, which orchestrate the onset and outcome of many host immune responses. Understanding which peptides will be presented by the MHC-II molecule is therefore important for understanding the activation of T helper cells and can be used to identify T-cell epitopes. We here present updated versions of two MHC class II peptide binding affinity prediction methods, NetMHCII and NetMHCIIpan...
January 6, 2018: Immunology
https://www.readbyqxmd.com/read/29314341/synthesis-of-galactosylated-glycosylphosphatylinositols-derivatives-from-trypanosoma-brucei
#14
Maurice Grube, Lee Bo-Young, Monika Garg, Dana Michel, Ankita Malik, Ivan Vilotijevic, Peter H Seeberger, Daniel Varon Silva
Trypanosoma brucei uses variant surface glycoproteins (VSGs) to evade the host immune system and ensure parasitic longevity in animals and humans. VSGs are attached to the cell membrane by complex glycosylphosphatidylinositol anchors (GPI). Distinguishing structural feature of VSG GPIs are multiple alpha and beta-galactosides attached to the conserved GPI core structure. T. brucei GPIs have been associated with macrophage activation and alleviation of parasitemia during infection, acting as disease onset delaying antigens...
January 3, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29313728/the-potential-of-currently-unavailable-herpes-virus-vaccines
#15
Július Rajcáni, Ferenc Bánáti, Kálmán Szenthe, Susan Szathmary
Despite overwhelming experimental work, there are no licensed vaccines against the most frequent Alphaherpesviruses, namely herpes simplex virus 1 and 2 (HSV1 and 2) nor against the Epstein-Barr virus (EBV), a member of the subfamily Gammaherpesvirus. Areas covered: Since the DNAs of both HSVs reside in the regional sensory ganglia in a latent state (i.e. as circularized episomal molecules), a corresponding vaccine might be useful for immunotherapy rather than prevention of primary infection. Here we describe the design of a purified subunit vaccine (a mix of at least 3 glycoproteins) as well as the preparation and efficacy of a recombinant fusion protein consisting of the gD ectodomain from our domestic attenuated HSV1 strain HSZP...
January 9, 2018: Expert Review of Vaccines
https://www.readbyqxmd.com/read/29313026/transcutaneous-pollinosis-immunotherapy-using-a-solid-in-oil-nanodispersion-system-carrying-t-cell-epitope-peptide-and-r848
#16
Momoko Kitaoka, Ayaka Naritomi, Yoshinori Kawabe, Masamichi Kamihira, Noriho Kamiya, Masahiro Goto
Antigen-specific immunotherapy is the only curative approach for the treatment of allergic diseases such as Japanese cedar pollinosis. Immunotherapy using a T cell epitope vaccine in combination with the adjuvant R848 is of particular interest as a safe and effective approach to treat allergic diseases. Herein, we propose a simple and easy to handle vaccine administration method using the original solid-in-oil (S/O) nanodispersion system that permeates through the skin. The S/O nanodispersion system is composed of nanoparticles of hydrophilic molecules surrounded with hydrophobic surfactants that are dispersed in an oil vehicle...
March 2017: Bioengineering & Translational Medicine
https://www.readbyqxmd.com/read/29310678/computational-analysis-of-envelope-glycoproteins-from-diverse-geographical-isolates-of-bovine-leukemia-virus-identifies-highly-conserved-peptide-motifs
#17
Aneta Pluta, Lorraine M Albritton, Marzena Rola-Łuszczak, Jacek Kuźmak
BACKGROUND: Bovine leukemia virus (BLV) is a deltaretrovirus infecting bovine B cells and causing enzootic bovine leucosis. The SU or surface subunit, gp51, of its envelope glycoprotein is involved in receptor recognition and virion attachment. It contains the major neutralizing and CD4+ and CD8+ T cell epitopes found in naturally infected animals. In this study, we aimed to determine global variation and conservation within gp51 in the context of developing an effective global BLV vaccine...
January 8, 2018: Retrovirology
https://www.readbyqxmd.com/read/29306566/bispecific-chimeric-antigen-receptors-targeting-the-cd4-binding-site-and-high-mannose-glycans-of-gp120-optimized-for-anti-human-immunodeficiency-virus-potency-and-breadth-with-minimal-immunogenicity
#18
Mustafa H Ghanem, Sara Bolivar-Wagers, Barna Dey, Agnes Hajduczki, Diego A Vargas-Inchaustegui, David T Danielson, Virgilio Bundoc, Li Liu, Edward A Berger
BACKGROUND AIMS: Chimeric antigen receptors (CARs) offer great potential toward a functional cure of human immunodeficiency virus (HIV) infection. To achieve the necessary long-term virus suppression, we believe that CARs must be designed for optimal potency and anti-HIV specificity, and also for minimal probability of virus escape and CAR immunogenicity. CARs containing antibody-based motifs are problematic in the latter regard due to epitope mutation and anti-idiotypic immune responses against the variable regions...
January 3, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29302635/supramolecular-peptide-nanofibers-engage-mechanisms-of-autophagy-in-antigen-presenting-cells
#19
Jai S Rudra, Arshad Khan, Tara M Clover, Janice J Endsley, Andrew Zloza, Jin Wang, Chinnaswamy Jagannath
Supramolecular peptide nanofibers are attractive for applications in vaccine development due to their ability to induce strong immune responses without added adjuvants or associated inflammation. Here, we report that self-assembling peptide nanofibers bearing CD4+ or CD8+ T cell epitopes are processed through mechanisms of autophagy in antigen-presenting cells (APCs). Using standard in vitro antigen presentation assays, we confirmed loss and gain of the adjuvant function using pharmacological modulators of autophagy and APCs deficient in multiple autophagy proteins...
December 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/29295593/structural-and-immunological-characterization-of-novel-recombinant-momp-based-chlamydial-antigens
#20
Guillermo Madico, Olga Gursky, Jeff Fairman, Paola Massari
Chlamydia is the most common cause of bacterial sexually transmitted infections worldwide. While infections resolve with antibiotic treatment, this is often neglected in women due to frequent asymptomatic infections, leading to disease progression and severe sequelae (pelvic inflammatory disease, ectopic pregnancy, infertility). Development of a vaccine against Chlamydia is crucial. Whole organism-based vaccines have short-lived activity, serovar/subgroup-specific immunity and can cause adverse reactions in vaccinated subjects...
December 25, 2017: Vaccines
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