DOCSLIB.ORG

Sclerosis Model HLA-DR15 and TCR Transgenic Multiple High Incidence of Spontaneous Disease in An

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Sclerosis Model HLA-DR15 and TCR Transgenic Multiple High Incidence of Spontaneous Disease in An High Incidence of Spontaneous Disease in an HLA-DR15 and TCR Transgenic Multiple Sclerosis Model This information is current as Stephan Ellmerich, Marcin Mycko, Katalin Takacs, of September 28, 2021. Hanspeter Waldner, Faisal N. Wahid, Rosemary J. Boyton, Rosalind H. M. King, Paul A. Smith, Sandra Amor, Amy H. Herlihy, Rachel E. Hewitt, Mark Jutton, David A. Price, David A. Hafler, Vijay K. Kuchroo and Daniel M. Altmann J Immunol 2005; 174:1938-1946; ; Downloaded from doi: 10.4049/jimmunol.174.4.1938 http://www.jimmunol.org/content/174/4/1938 References This article cites 36 articles, 11 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/174/4/1938.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 28, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology High Incidence of Spontaneous Disease in an HLA-DR15 and TCR Transgenic Multiple Sclerosis Model1 Stephan Ellmerich,* Marcin Mycko,§ Katalin Takacs,* Hanspeter Waldner,§ Faisal N. Wahid,* Rosemary J. Boyton,* Rosalind H. M. King,¶ Paul A. Smith,† Sandra Amor,† Amy H. Herlihy,‡ Rachel E. Hewitt,ʈ Mark Jutton,* David A. Price,# David A. Hafler,§ Vijay K. Kuchroo,§ and Daniel M. Altmann2* Multiple sclerosis (MS) is thought to involve CD4 T cell recognition of self myelin, many studies focusing on a pathogenic role for anti-myelin, HLA-DR15-restricted T cells. In experimental allergic encephalomyelitis, it is known which epitopes trigger disease and that disease is associated with determinant spread of T cell reactivity. Characterization of these events in human MS is critical for the development of peptide immunotherapies, but it has been difficult to define the role of determinant spread or define which Downloaded from epitopes might be involved. In this study, we report humanized transgenic mice, strongly expressing HLA-DR15 with an MS- derived TCR; even on a RAG-2 wild-type background, mice spontaneously develop paralysis. Disease, involving demyelination and axonal degeneration, correlates with inter- and intramolecular spread of the T cell response to HLA-DR15-restricted epitopes of myelin basic protein, myelin oligodendrocyte glycoprotein, and ␣B-crystallin. Spread is reproducible and progressive, with two of the epitopes commonly described in responses of HLA-DR15 patients. The fact that this pattern is reiterated as a consequence of CNS tissue damage in mice demonstrates the value of the transgenic model in supplying an in vivo disease context for the human responses. This http://www.jimmunol.org/ model, encompassing pathologically relevant, spontaneous disease with the presentation of myelin epitopes in the context of HLA-DR15, should offer new insights and predictions about T cell responses during MS as well as a more stringent test bed for immunotherapies. The Journal of Immunology, 2005, 174: 1938–1946. xperimental allergic encephalomyelitis (EAE)3 is a pro- are abundant data on the specific T cell responses that must be totypic model of autoimmunity in which many basic te- targeted to alleviate disease, while in human studies, in which a E nets of autoimmune disease originate (1). Efforts to im- multitude of T cell epitopes is implicated, this is not the case. An plement peptide-based immunotherapies for multiple sclerosis additional problem is that, in many EAE models, disease progres- (MS) aim to build on the large dataset of EAE tolerogenic and sion is associated with spread of T cell responses, although de- by guest on September 28, 2021 antagonist peptide therapies (2, 3). However, translation from a pendence of disease on spread differs somewhat between EAE peptide-induced murine model to the complex pattern of myelin models, raising questions about the generality of this effect in CNS responses found in humans with a spontaneous and variable dis- disease (4–7). The role of epitope spread in relapsing and remitting ease such as MS offers a daunting challenge. In mouse EAE, there MS is unclear. Heterogeneity in HLA genotype and disease phe- notype and the long timescale of disease progression make this *Human Disease Immunogenetics Group, Department of Infectious Diseases and difficult to study (8, 9). An appreciation of the nature and extent of Transplantation Biology Group, Medical Research Council Clinical Sciences Centre, epitope spread in MS will be critical to the successful development † Imperial College, Hammersmith Hospital, London, United Kingdom; Department of of peptide therapies, which may need to be different in patients Neuroinflammation, Division of Neuroscience, Imperial College and Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands; with long-term compared with recent onset disease (10). ‡Biological Imaging Centre, Medical Research Council Clinical Sciences Centre, Im- § The response against myelin basic protein (MBP) 83–99 is an perial College, London, United Kingdom; Center for Neurologic Diseases, Brigham ϩ and Women’s Hospital, Harvard Medical School, Boston, MA 02115; ¶Department of immunodominant one in DR15 MS patients (11), while compar- Clinical Neurosciences, Royal Free and University College Medical School, London, ʈ ison of T cell responses to myelin from normal and MS brain United Kingdom; Peter Medawar Building for Pathogen Research, University of ␣ Oxford, Oxford, United Kingdom; and #Vaccine Research Center, National Institute emphasizes the importance of responses to B-crystallin in MS- of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD derived tissue (12). Furthermore, ␣B-crystallin is one of the most 20892 abundantly induced transcripts in MS brain (13). Other compari- Received for publication September 14, 2004. Accepted for publication November sons of T cell responses from patients and controls identify 11, 2004. epitopes from myelin oligodendrocyte glycoprotein (MOG) and The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance proteolipoprotein (14, 15). with 18 U.S.C. Section 1734 solely to indicate this fact. An optimal MS model for addressing these issues would be 1 This work was funded by grants from the Multiple Sclerosis Society of Great Britain spontaneous, introducing no inherent bias through being rooted in and Northern Ireland and the Biotechnology and Biological Sciences Research particular modes of EAE induction, would be pathologically se- Council. vere and faithful to the human disease, and would be immunoge- 2 Address correspondence and reprint requests to Dr. Daniel M. Altmann, Human Disease Immunogenetics Group, Department of Infectious Diseases, Imperial Col- netically humanized. In this way, HLA-restricted epitopes impli- lege, Hammersmith Hospital, Du Cane Road, London W12 ONN, U.K. E-mail ad- cated in disease progression or amelioration in the reductionist dress: [email protected] context of the mouse model could be readily investigated in the 3 Abbreviations used in this paper: EAE, experimental allergic encephalomyelitis; MBP, myelin basic protein; MOG, myelin oligodendrocyte glycoprotein; MS, mul- human setting. One of the first reported TCR transgenic disease tiple sclerosis; PNS, peripheral nervous system; SP, single positive. models involving expression of a murine EAE-derived TCR Copyright © 2005 by The American Association of Immunologists, Inc. 0022-1767/05/$02.00 The Journal of Immunology 1939 showed a high incidence of spontaneous disease that was depen- 5 ϫ 103 per well with CD4ϩ or CD8ϩ effector cells. At 4 h, supernatants dent to some extent on the environment in which the mice were were removed from each well for counting in an automated gamma housed (16). The immunogenetics of human MS have previously counter. Specific lysis was calculated according to the formula: (mean sam- ple cpm Ϫ mean spontaneous release)/(mean total cpm Ϫ mean sponta- been modeled by expressing HLA class II genes, or HLA-DR with neous release) ϫ 100. a matched TCR, in transgenic mice (17–20). Disease in HLA-DR/ TCR transgenics has been achieved by injection of myelin peptides Paralysis scores under EAE-inducing conditions or by crossing onto RAG-2 knock- Mice were scored for spontaneous disease, as follows: 0, normal; 1, limp outs, eliminating T regulatory cells, although a high incidence of tail; 2, impaired righting reflex or waddling gait; 3, partial hind limb pa- spontaneous disease in humanized models has rarely been ob- ralysis; 4, total hind limb paralysis; 5, total limb paralysis; 6, moribund. served. In this study, we describe a unique model in which there is Histopathology a very high incidence of spontaneous disease, allowing the analysis of CNS pathology that is faithful to clinical
Load more

Recommended publications
  • 1 Polymorphisms in Brucella Carbonic Anhydrase II Mediate CO2 Dependence and Fitness 1 in Vivo. 2 3 García-Lobo JM1, Ortiz Y1
    bioRxiv preprint doi: https://doi.org/10.1101/804740; this version posted October 15, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Polymorphisms in Brucella Carbonic anhydrase II mediate CO2 dependence and fitness 2 in vivo. 3 4 García-Lobo JM1, Ortiz Y1, González-Riancho C1, Seoane A1, Arellano-Reynoso B2, and 5 Sangari FJ1* 6 7 *Corresponding author 8 1. Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), CSIC-Universidad de 9 Cantabria, and Departamento de Biología Molecular, Universidad de Cantabria, 39011 10 Santander, Spain. 11 2. Departamento de Microbiología, Facultad de Medicina Veterinaria y Zootecnia, Universidad 12 Nacional Autónoma de México, Circuito Exterior de Ciudad Universitaria, Delegación 13 Coyoacán, Mexico City, C.P. 04510, Mexico. 14 15 FJS conceived and coordinated the study, conducted bacteriology work and wrote the 16 manuscript. JMGL analyzed the data and wrote the manuscript. YO, CGR, AS and BAR 17 conducted bacteriology work. All authors interpreted the data, corrected the manuscript, and 18 approved the content for publication. 19 20 21 Keywords. Brucella, Carbonic anhydrase, CO2 requirement, fitness, protein structure 22 1 bioRxiv preprint doi: https://doi.org/10.1101/804740; this version posted October 15, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 23 Abstract 24 25 Some Brucella isolates are known to require an increased concentration of CO2 for growth, 26 especially in the case of primary cultures obtained directly from infected animals.
    [Show full text]
  • RELEVANCE of Tolc and EXPRESSION OF
    RELEVANCE OF tolC AND EXPRESSION OF acrAB AND emrAB IN Erwinia chrysandiemi by RAVI DAMODAR BARABOTE, B.Sc, M.Sc. A DISSERTATION IN BIOLOGY Submitted to the Graduate Faculty of Texas Tech University in Partial Fulfillment of the Requirements for die Degree of DOCTOR OF PHILOSOPHY Approved Chai/person of the Committee I •~A \S i * "». Accepted ^ •-'- • • f ^^ ^ ..I y I Dean of the Graduate School December, 2003 ACKNOWLEDGEMENTS This dissertation is dedicated in the loving memory of my mom, Pratibha Barabote, and to my dad, Damodar Barabote, who epitomize unconditional love. They worked very hard and sacrificed many things in order to help me achieve my goals. My interactions with Dr. Michael San Francisco have tiansformed me into a wiser and more self-confident student. He has served as a constant source of inspiration for me and I have leamt a great deal from him, in explicit as well as imphcit ways. He went out of his way to help me in any way he could, even beyond the frontiers of professional hfe. His faith in my skills always boosted my confidence. I would like to express my smcere gratitude to Dr. San Francisco for all his help and support. He is an extiaordinarily understandmg and a nice individual. I extend my heartfelt thanks to him for his mcredible patience, constant encouragement, and support throughout my doctoral work. I sincerely thank him for fmancially supporting me with a research assistantship during several semesters. This work would not be possible without the sustained support of my doctoral committee members, who have also been a great source of inspiration for me.
    [Show full text]
  • Monoamine Oxidase-A Physically Interacts with Presenilin-1(M146V) in the Mouse Cortex
    Journal of Alzheimer’s Disease 28 (2012) 403–422 403 DOI 10.3233/JAD-2011-111241 IOS Press Monoamine Oxidase-A Physically Interacts with Presenilin-1(M146V) in the Mouse Cortex Zelan Weia, Geraldine G. Gabriela, Lewei Ruia, Xia Caoa, Paul R. Penningtona, Jennifer Chlan-Fourneyb, Adil J. Nazaralic, Glen B. Bakerd and Darrell D. Mousseaua,∗ aCell Signalling Laboratory, Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada bDepartment of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Canada cLaboratory of Molecular Cell Biology, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Canada dNeurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, Canada Accepted 8 September 2011 Abstract. The concentration of presenilin-1 (PS-1) protein at the mitochondrial-associated aspect of the endoplasmic reticulum supports the potential for a mitochondrial influence of PS-1. Given that carriers of certain Alzheimer’s disease (AD)-related PS-1 variants are predisposed to clinical depression and that depression has been historically associated with the mitochondrial enzyme, monoamine oxidase-A (MAO-A), we investigated cortical MAO-A function in the AD-related PS-1(M146V) knock-in mouse. The MAO-A system was clearly altered in the PS-1(M146V) mouse as revealed by (a) a mismatch between MAO-A protein expression and MAO-A activity; (b) changes in MAO-A-mediated monoaminergic neurotransmitter metabolism; (c) changes in non-cognitive behavior following treatment with the irreversible MAO-A inhibitor clorgyline; and (d) an increase in the potency of clorgyline in these same mice. We next investigated whether PS-1(M146V) could be influencing MAO-A directly.
    [Show full text]
  • Investigation Into the Role of Phosphatidylserine in Modifying the Susceptibility of Human Lymphocytes to Secretory Phospholipas
    Biochimica et Biophysica Acta 1818 (2012) 1196–1204 Contents lists available at SciVerse ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbamem Investigation into the role of phosphatidylserine in modifying the susceptibility of human lymphocytes to secretory phospholipase A2 using cells deficient in the expression of scramblase Jennifer Nelson, Lyndee L. Francom, Lynn Anderson, Kelly Damm, Ryan Baker, Joseph Chen, Sarah Franklin, Amy Hamaker, Izadora Izidoro, Eric Moss, Mikayla Orton, Evan Stevens, Celestine Yeung, Allan M. Judd, John D. Bell ⁎ Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah 84602, USA article info abstract Article history: Normal human lymphocytes resisted the hydrolytic action of secretory phospholipase A2 but became susceptible Received 8 September 2011 to the enzyme following treatment with a calcium ionophore, ionomycin. To test the hypothesis that this suscep- Received in revised form 22 November 2011 tibility requires exposure of the anionic lipid phosphatidylserine on the external face of the cell membrane, Accepted 9 January 2012 experiments were repeated with a human Burkitt's lymphoma cell line (Raji cells). In contrast to normal lympho- Available online 13 January 2012 cytes or S49 mouse lymphoma cells, most of the Raji cells (83%) did not translocate phosphatidylserine to the cell surface upon treatment with ionomycin. Those few that did display exposed phosphatidylserine were hydro- Keywords: Secretory phospholipase A2 lyzed immediately upon addition of phospholipase A2. Interestingly, the remaining cells were also completely Phosphatidylserine exposure susceptible to the enzyme but were hydrolyzed at a slower rate and after a latency of about 100 s. In contradis- Biophysical membrane change tinction to the defect in phosphatidylserine translocation, Raji cells did display other physical membrane changes Hydrolysis upon ionomycin treatment that may be relevant to hydrolysis by phospholipase A2.
    [Show full text]
  • An Investigation of the Stem Cell Potential of Skeletal Muscle Satellite Cells
    An investigation of the stem cell potential of skeletal muscle satellite cells Charlotte Anne Collins Eastman Dental Institute University College London A thesis submitted to the University of London in fulfilment of the requirements for the degree of Doctor of Philosophy September 2004 UMI Number: U602529 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. Dissertation Publishing UMI U602529 Published by ProQuest LLC 2014. Copyright in the Dissertation held by the Author. Microform Edition © ProQuest LLC. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Abstract Satellite cells are defined by their position beneath the basal lamina of myofibres, and are a source of new myonuclei in adult skeletal muscles. However, other phenotypes also contribute to muscle regeneration, and the relative importance of satellite cells is not known. This work aimed to analyse the stem cell potential of,satellite cells by formally investigating their contribution to muscle regeneration. Myofibres isolated from extensor digitorum longus, soleus, and tibialis anterior muscles were found to have respective means of 7, 22 and 10 associated satellite cells. When a single myofibre was grafted into an irradiated dystrophic mouse muscle, the associated satellite cells underwent extensive, stem cell-like proliferation, generating progeny which sometimes gave rise to a cluster of more than 100 new myofibres.
    [Show full text]
  • Influences of Gravitational Intensity on the Transcriptional Landscape of Arabidopsis
    Influences of Gravitational Intensity on the Transcriptional Landscape of Arabidopsis thaliana A dissertation presented to the faculty of the College of Arts and Sciences of Ohio University In partial fulfillment of the requirements for the degree Doctor of Philosophy Alexander D. Meyers May 2020 © 2020 Alexander D. Meyers. All Rights Reserved. 2 This dissertation titled Influences of Gravitational Intensity on the Transcriptional Landscape of Arabidopsis thaliana by ALEXANDER D. MEYERS has been approved for the Department of Molecular and Cellular Biology and the College of Arts and Sciences by Sarah E. Wyatt Professor of Environmental and Plant Biology Florenz Plassmann Dean, College of Arts and Sciences 3 Abstract MEYERS, ALEXANDER D, Ph.D., May 2020, Molecular and Cellular Biology Influences of Gravitational Intensity on the Transcriptional Landscape of Arabidopsis thaliana Director of Dissertation: Sarah E. Wyatt Plants use a myriad of environmental cues to inform their growth and development. The force of gravity has been a consistent abiotic input throughout plant evolution, and plants utilize gravity sensing mechanisms to maintain proper orientation and architecture. Despite thorough study, the specific mechanics behind plant gravity perception remain largely undefined or unproven. At the center of plant gravitropism are dense, specialized organelles called starch statoliths that sediment in the direction of gravity. Herein I describe a series of experiments in Arabidopsis that leveraged RNA sequencing to probe gravity response mechanisms in plants, utilizing reorientation in Earth’s 1g, fractional gravity environments aboard the International Space Station, and simulated fractional and hyper gravity environments within various specialized hardware. Seedlings were examined at organ-level resolution, and the statolith-deficient pgm-1 mutant was subjected to all treatments alongside wildtype seedlings in an effort to resolve the impact of starch statoliths on gravity response.
    [Show full text]
  • Susceptibility of Apoptotic Cells to Hydrolysis by Spla2: Molecular Basis and Mechanisms Defined
    Brigham Young University BYU ScholarsArchive Theses and Dissertations 2013-07-05 Susceptibility of Apoptotic Cells to Hydrolysis by sPLA2: Molecular Basis and Mechanisms Defined Elizabeth Gibbons Brigham Young University - Provo Follow this and additional works at: https://scholarsarchive.byu.edu/etd Part of the Cell and Developmental Biology Commons, and the Physiology Commons BYU ScholarsArchive Citation Gibbons, Elizabeth, "Susceptibility of Apoptotic Cells to Hydrolysis by sPLA2: Molecular Basis and Mechanisms Defined" (2013). Theses and Dissertations. 3690. https://scholarsarchive.byu.edu/etd/3690 This Dissertation is brought to you for free and open access by BYU ScholarsArchive. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of BYU ScholarsArchive. For more information, please contact [email protected], [email protected]. Susceptibility of Apoptotic Cells to Hydrolysis by sPLA2: Molecular Basis and Mechanisms Defined Elizabeth Gibbons A dissertation submitted to the faculty of Brigham Young University in partial fulfillment of the requirements for the degree of Doctor of Philosophy John D. Bell, Chair Allan M. Judd Sandra H. Burnett Michael R. Stark Laura C. Bridgewater Department of Physiology and Developmental Biology Brigham Young University July 2013 Copyright © 2013 Elizabeth Gibbons All Rights Reserved ABSTRACT Susceptibility of Apoptotic Cells to Hydrolysis by sPLA2: Molecular Basis and Mechanisms Defined Elizabeth Gibbons Department of Physiology and Developmental Biology, BYU Doctor of Philosophy Secretory phospholipase A2 hydrolyzes phospholipids at a lipid-water interface, resulting in pro-inflammatory products being released from cell membranes. Healthy cells are resistant to cleavage by this enzyme, but apoptotic cells become susceptible to its activity. Only bilayers with certain characteristics are able to be hydrolyzed.
    [Show full text]
  • BC-Afacan-2013.Pdf
    Progress in Inflammation Research Series Editors Michael J. Parnham, University Hospital for Infectious Diseases, Zagreb, Croatia Eugen Faist, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany Advisory Board G.Z. Feuerstein (Wyeth Research, Collegeville, PA, USA) M. Pairet (Boehringer Ingelheim Pharma KG, Biberach a. d. Riss, Germany) W. van Eden (Universiteit Utrecht, Utrecht, The Netherlands) For further volumes: http://www.springer.com/series/4983 . Pieter S. Hiemstra • Sebastian A. J. Zaat Editors Antimicrobial Peptides and Innate Immunity Editors Pieter S. Hiemstra Sebastian A. J. Zaat Department of Pulmonology Dept. Medical Microbiology Leiden University Medical Center Ctr for Infection & Immun. Amsterdam Leiden (CINIMA) Netherlands Academic Medical Center University of Amsterdam Amsterdam Netherlands Series Editors Prof. Michael J. Parnham, Ph.D. Prof. Eugen Faist, MD, FACS Visiting Scientist Ludwig-Maximilians-University Munich Research & Clinical Immunology Unit Klinikum Grosshadern University Hospital for Infectious Diseases Department of Surgery “Dr. Fran Mihaljevic´” Marchioninistr. 15 Mirogojska 8 81377 Munich HR-10000 Zagreb, Croatia Germany ISBN 978-3-0348-0540-7 ISBN 978-3-0348-0541-4 (eBook) DOI 10.1007/978-3-0348-0541-4 Springer Basel Heidelberg New York Dordrecht London Library of Congress Control Number: 2012956531 # Springer Basel 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation,
    [Show full text]
  • A Peptide-Based Platform for Displaying Antibodies to Engage T Cells Ying Zheng
    Duquesne University Duquesne Scholarship Collection Electronic Theses and Dissertations Fall 2010 A Peptide-Based Platform for Displaying Antibodies to Engage T Cells Ying Zheng Follow this and additional works at: https://dsc.duq.edu/etd Recommended Citation Zheng, Y. (2010). A Peptide-Based Platform for Displaying Antibodies to Engage T Cells (Doctoral dissertation, Duquesne University). Retrieved from https://dsc.duq.edu/etd/1412 This Immediate Access is brought to you for free and open access by Duquesne Scholarship Collection. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of Duquesne Scholarship Collection. For more information, please contact [email protected]. A PEPTIDE-BASED PLATFORM FOR DISPLAYING ANTIBODIES TO ENGAGE T CELLS A Dissertation Submitted to the Graduate School of Pharmaceutical Sciences Duquesne University In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Pharmaceutics By Ying Zheng December 2010 Copyright by Ying Zheng 2010 A PEPTIDE-BASED PLATFORM FOR DISPLAYING ANTIBODIES TO ENGAGE T CELLS By Ying Zheng Approved October 14, 2010 _________________________________ ___________________________________ Wilson S. Meng, Ph.D. James K. Drennen, III, Ph.D. Associate Professor of Pharmaceutical Associate Professor of Pharmaceutics Sciences Associate Dean for Graduate Programs and (Committee Chair) Research (Committee Member) __________________________________ ___________________________________ Philip E. Auron, Ph.D Ellen Gawalt, Ph.D Professor and Chair of Biological Sciences Associate Professor of Chemistry and Biochemistry (Committee Member) (Committee Member) __________________________________ ___________________________________ Peter Wildfong, Ph.D J. Douglas Bricker, Ph.D Associate Professor of Pharmaceutics Professor of Pharmacology-Toxicology (Committee Member) Dean of the Mylan School of Pharmacy iii ABSTRACT A PEPTIDE-BASED PLATFORM FOR DISPLAYING ANTIBODIES TO ENGAGE T CELLS By Ying Zheng December 2010 Dissertation supervised by Wilson S.
    [Show full text]
  • Electronic Supplementary Information S9
    Electronic Supplementary Material (ESI) for Metallomics. This journal is © The Royal Society of Chemistry 2019 Electronic Supplementary Information S9 . Changes in gene expression due to As III exposure in the contrasting hairy roots. HYBRIDIZATION 1: LIST OF UP-REGULATED GENES Fold Change Probe Set ID ([0.1.HR] vs [0.HR]) Blast2GO description Genbank Accessions Serine/threonine -protein phosphatase 7 long form BT2M444_at 101.525 homolog AJ538927 DV159578_at 67.016 Retrotransposon Tnt1 s231d long terminal repeat DV159578 EB427540_at 49.6314 DNA repair metallo-beta-lactamase family protein EB427540 C3356_at 39.8605 Late embryogenesis abundant domain-containing protein DV157779 C7375_at 39.0452 wall-associated serine threonine kinase BP525596 C11724_at 37.103 5' exonuclease Apollo-like, transcript variant 2 AJ718369 EB682553_at 36.7071 EIF4A-2 EB682553 U92011_at 34.5134 apocytochrome b U92011 C5842_at 33.8783 heat shock protein 90 EB432766 AF211619_at 31.8765 AF211619 BC1M4448_s_at 31.2217 AJ538430 TT39_L17_at 29.7963 lysine-ketoglutarate reductase EB429701_at 29.3945 EB429701 BP137485_at 29.0749 Retrotransposon Tnt1 s231d long terminal repeat BP137485 CV021716_at 28.8452 Plastocyanin-like domain-containing protein CV021716 DW002835_at 27.8539 peroxidase DW002835 EB429725_at 27.6171 Carbonic anhydrase, transcript variant 1 (ca1), mRNA EB429725 TT19_B11_at 26.3284 50s ribosomal protein l16 DV158314_at 24.4108 DV158314 C7180_at 23.668 cytochrome oxidase subunit i BP528067 EB445091_at 22.6679 lysine-ketoglutarate reductase EB445091 GC227C_at
    [Show full text]
  • Conserved Molecular Signatures of Neurogenesis in the Hippocampal Subgranular Zone of Rodents and Primates Jeremy A
    © 2013. Published by The Company of Biologists Ltd | Development (2013) 140, 4633-4644 doi:10.1242/dev.097212 RESEARCH ARTICLE TECHNIQUES AND RESOURCES Conserved molecular signatures of neurogenesis in the hippocampal subgranular zone of rodents and primates Jeremy A. Miller1, Jason Nathanson2, Daniel Franjic3, Sungbo Shim3, Rachel A. Dalley1, Sheila Shapouri1, Kimberly A. Smith1, Susan M. Sunkin1, Amy Bernard1, Jeffrey L. Bennett4, Chang-Kyu Lee1, Michael J. Hawrylycz1, Allan R. Jones1, David G. Amaral4, Nenad Šestan3, Fred H. Gage2 and Ed S. Lein1,* ABSTRACT adult SGZ and SVZ are likely to be multipotent (Temple, 2001), and The neurogenic potential of the subgranular zone (SGZ) of the these niches utilize many of the signals and morphogens expressed hippocampal dentate gyrus is likely to be regulated by molecular cues during development, such as Notch, sonic hedgehog (SHH), bone arising from its complex heterogeneous cellular environment. morphogenetic proteins (BMPs) and noggin (Alvarez-Buylla and Through transcriptome analysis using laser microdissection coupled Lim, 2004). Adult neurogenesis has been observed in many with DNA microarrays, in combination with analysis of genome-wide mammals, including mice, rats, rabbits, hamsters, dogs, monkeys in situ hybridization data, we identified 363 genes selectively enriched and humans (Amrein et al., 2011; Eriksson et al., 1998), and the rate in adult mouse SGZ. These genes reflect expression in the different of neurogenesis and the survival of newly generated neurons can be constituent cell types, including progenitor and dividing cells, modulated by behavior and external environment (van Praag et al., immature granule cells, astrocytes, oligodendrocytes and GABAergic 1999). interneurons. Similar transcriptional profiling in the rhesus monkey Similar processes have been described in the SGZ and SVZ of dentate gyrus across postnatal development identified a highly mice, including a sequential progression through progenitor types overlapping set of SGZ-enriched genes, which can be divided based during neurogenesis.
    [Show full text]
  • Protein Mixtures of Environmental Friendly Zein to Understand Protein
    Physical Chemistry Chemical Physics Protein Mixtures of Environmental Friendly Zein to understand Protein – Protein Interactions through Biomaterials Synthesis, Hemolysis, and their Antimicrobial Activities Journal: Physical Chemistry Chemical Physics Manuscript ID: CP-ART-04-2014-001457.R1 Article Type: Paper Date Submitted by the Author: 20-May-2014 Complete List of Authors: Bakshi, Mandeep Singh; WLU, Chemistry Mahal, Aabroo; DAV, Chemistry Kumar, Manoj; DAV, Chemistry Khullar, Poonam; DAV, Chemistry Kaur, Gurinder; CNA, Singh, Narinder; Indian Institute of Technology Ropar, Chemistry Kumar, Harsh; National Institute of Technology, Chemistry Page 1 of 34 Physical Chemistry Chemical Physics Protein Mixtures of Environmental Friendly Zein to understand Protein – Protein Interactions through Biomaterials Synthesis, Hemolysis, and their Antimicrobial Activities Aabroo Mahal 3,4 , Manoj Kumar Goshisht 3,4 , Poonam Khullar 3, Harsh Kumar 4, Narinder Singh 5, Gurinder Kaur 2, Mandeep Singh Bakshi 1* 1Department of Chemistry, Wilfrid Laurier University, Science Building, 75 University Ave. W., Waterloo ON N2L 3C5, Canada, 2Nanotechnology Research Laboratory, College of North Atlantic, Labrador City, NL A2V 2K7 Canada, 3Department of Chemistry, B.B.K. D.A.V. College for Women, Amritsar 143005, Punjab, India, 4Department of Chemistry, Dr. B. R. Ambedkar National Institute of Technology, Jalandhar-144011, Punjab, India. 5Department of Chemistry, Indian Institute of Technology Ropar, Rupnagar-140001, Punjab, India. First two authors have equal contribution. Abstract Industrial important zein protein has been employed to understand its interactions with two model proteins bovine serum albumin (BSA) and cytochrome c (Cyc,c) following the in vitro synthesis of Au NPs so as to expand its applicability for biological applications. Interactions were studied under the effect of temperature variation by using UV-visible and fluorescence emission studies.
    [Show full text]