DOCSLIB.ORG

Identifying Epitopes of Hiv-1 That Induce Protective Antibodies

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Identifying Epitopes of Hiv-1 That Induce Protective Antibodies REVIEWS IDENTIFYING EPITOPES OF HIV-1 THAT INDUCE PROTECTIVE ANTIBODIES Susan Zolla-Pazner During the past 20 years, the pendulum of opinion in the HIV-1 vaccine field has swung between two extremes, initially favouring the induction of antibodies only, and subsequently favouring the induction of cell-mediated immune responses only. At present, the consensus seems to be that induction of both humoral and cellular immunity by an HIV-1 vaccine will be required to achieve maximum protection. One obstacle to the development of an effective HIV-1 vaccine has been the difficulty in inducing broadly reactive, potent antibodies with protective functions. Defining epitopes and designing immunogens that will induce these antibodies is one of the main challenges that now confronts the HIV-1 vaccine field. ACTIVE IMMUNIZATION Although cell-mediated immunity is crucial for control- ever be able to induce antibodies that are sufficiently The induction of immunity ling and eradicating infection by many viruses, antibodies broad and potent to provide protection. Many passive with immunogens that activate are pivotal in preventing or modulating infection1,2.Even immunization experiments in various experimental and expand the endogenous during early phases of infection, when the level of anti- models have, however, repeatedly established that immune repertoire, eliciting antibodies and cell-mediated bodies induced by ACTIVE IMMUNIZATION or administered antibodies can provide sterilizing immunity against immunity, as well as by PASSIVE IMMUNIZATION is low, antibodies can reduce the HIV-1 (REFS 6–9).In addition, passive immunization immunological memory that size of the infecting inoculum and neutralize or elimi- experiments indicate that antibodies reduce the size of might last for decades. nate virions during the first rounds of replication. This the infectious inoculum and allow the development PASSIVE IMMUNIZATION provides sufficient transient protection so that the of more effective cellular and humoral immune Immunity that is provided cellular arm of the immune response can respond with responses to the breakthrough virus3.These studies rapidly by the transfer of proliferation and deployment of effector T cells that are provide convincing data in all of the experimental immunoglobulins, the maximal activity of which lasts for ~2–3 required to eliminate virus-infected cells. Data indicate models tested that neutralizing antibodies with weeks before it wanes due to that this model is applicable to infection with HIV-1, appropriate specificity — when present in sufficient catabolic destruction. simian immunodeficiency virus (SIV) and the chimeric concentrations — are a correlate of immune protec- simian/human immunodeficiency virus (SHIV)3–5. tion. Even in humans, some studies indicate that anti- Despite extensive data supporting the general bodies transferred across the placenta might protect importance of antibodies in preventing virus infec- against transmission of HIV-1 from infected pregnant tions (FIG. 1),perceptions about the role of antibodies women to their infants10,11, although more studies of in preventing infection with HIV-1 have varied this controversial issue in humans are required. New York Veterans Affairs markedly over the past 20 years. Opinions have ranged Medical Center and NYU from the wildly optimistic views held in the late 1980s Protective mechanisms of antibodies School of Medicine, that antibodies would be sufficient to protect against Antibodies can protect against virus infection by many NewYork 10016, USA. infection, to the bleakest predictions of the mid-1990s mechanisms (FIG. 1).The main mode of protection that e-mail: zollas01@endeavor. med.nyu.edu that primary isolates were resistant to antibody- is induced by most antiviral vaccines seems to be doi:10.1038/nri1307 mediated neutralization and that no vaccine would mediated by neutralizing antibodies1.Neutralization NATURE REVIEWS | IMMUNOLOGY VOLUME 4 | MARCH 2004 | 199 © 2004 Nature Publishing Group REVIEWS e Complement- induced virolysis e Aggregation of infectious virions d Interruption of virus assembly a Blockade of virus– and maturation target-cell interaction d Inhibition b Blockade of post- of virus attachment stages budding Virus Viral proteins receptors d Prevention of Translation virus uncoating RNA Fusion Linear DNA Reverse transcription and nuclear import RNA c Inhibition of virus–cell fusion Transcription Figure 1 | Steps at which antibodies can potentially interfere with virus replication, using HIV-1 as an example. a | Antibodies can block the virus–target-cell interaction by several mechanisms, such as by: inhibiting the interaction of cell-derived molecules (such as adhesion molecules and lectins) carried in the virus envelope with their ligands on the surface of target cells; inhibiting the binding of virions to CD4 and co-receptors on the cell surface; and preventing conformational changes of the virus envelope that are required for subsequent steps in the virus life cycle. b | After attachment of the virus to target cells, antibodies can inhibit further conformational changes in the virus envelope glycoproteins that create or expose domains involved in virus–target-cell fusion. c | Antibodies can also block the protein domains that are involved in virus–cell fusion. d | At later stages in the virus life cycle, antibodies might be involved in: preventing virus uncoating after entry; interrupting virus assembly; preventing maturation of the virus particle; and inhibiting virus budding. e | Additional mechanisms of antibody-mediated neutralization include complement-induced virolysis and aggregation of infectious virions. is a generic term for the ability of antibodies to reduce has not yet been shown for HIV-1), blocking late the infectivity of a virus particle by interfering at one stages in the virus life cycle12.Therefore, antibodies of several different steps in the virus life cycle. For can prevent the primary uncoating of the virus in the example, antibodies can bind to molecules on the sur- cytoplasm, transcription steps in the nucleus, and face of virions and prevent their interaction with cell- virus assembly and budding at the cell membrane as surface lectins and with various receptors12,13.In the the virus exits the cell. case of HIV-1, this type of inhibition is attributed to Additional mechanisms by which antibodies can carbohydrate-specific antibodies that target the virus mediate protection include aggregation of virus parti- glycoproteins14,15,to antibodies that target different cles, which reduces the size of the inoculum and ren- adhesion molecules16, and to antibodies that are specific ders virions more susceptible to phagocytosis and for various regions of gp120 such as the CD4-binding destruction12, and lysis of enveloped viruses by binding domain, the ‘CD4-induced (CD4i) epitope’ (located to the virion and initiating the complement cascade22. in the bridging sheet of gp120 that is created or Antibodies might also attack virus-infected cells; for exposed when gp120 interacts with CD4)17, and the example, antibody-dependent cell-mediated cytotoxicity V2 and V3 loops (see FIG. 2 and BOX 1). In addition, (ADCC) is a well-documented antiviral mechanism many ‘post-attachment’ mechanisms have been docu- that controls virus infection, which has been shown to mented. An example of this is provided by antibodies affect HIV-1-infected cells23,24. that prevent the fusion of virus and cell membranes. In the case of HIV-1, the human monoclonal anti- Identification of protective epitopes body 2F5 (described later) might be such an antibody, Given the ‘rediscovered’ importance of antibodies in the preventing either the formation of the gp41 coiled- prevention of HIV-1 infection25, it is necessary to re- coil form or the fusion of virus and the cell examine the question of which antibodies should be membrane18–21.Antibodies can also mediate post- induced and how this might be achieved. As the most fusion neutralization of many viruses (although this consistent correlate of immune protection against viral 200 | MARCH 2004 | VOLUME 4 www.nature.com/reviews/immunol © 2004 Nature Publishing Group REVIEWS infections is the presence of neutralizing antibodies1,12, Constant regions of the virus envelope as targets emphasis has been placed on identifying antibodies that Antibodies to epitopes in gp41. Several human mono- neutralize HIV-1. clonal antibodies specific for gp41 have been produced, As with most pathogens, HIV-1 induces a poly- and several epitopes within gp41 have been defined27,30,31 clonal antibody response to a wide array of epitopes (FIG. 3, TABLE 1 and BOX 1). However, only a small minority on different viral proteins26,27.Studies of polyclonal of gp41-specific antibodies have neutralizing activity. sera have helped to identify the specificities of anti- One human monoclonal antibody, 2F5, has been shown bodies that are associated with protection28,29,but it is to have broad neutralizing activity for diverse primary the study of human monoclonal antibodies that has HIV-1 isolates32.This monoclonal antibody recognizes most clearly defined the few epitopes that are located a core epitope of six amino acids within a relatively in the two envelope glycoproteins, gp120 and gp41, conserved 16-amino-acid linear sequence (NEQEL- that induce neutralizing antibodies in natural infec- LELDKWASLWN) in the ectodomain of gp41 near the tion (TABLE 1) and mediate protection against infection transmembrane region of the molecule33.Two
Load more

Recommended publications
  • Rapid Mimotope Optimization for Pharmacokinetic Analysis of the Novel Therapeutic Antibody IMAB362 M
    APPLICATION NOTE PepStar™ Peptide Microarrays IMMUNOLOGY Rapid Mimotope Optimization for Pharmacokinetic Analysis of the Novel Therapeutic Antibody IMAB362 M. Daneschdar*, H.U. Schmoldt*, L. M. Plum**, Y. Kühne**, M. Fiedler*, A. Masch***, K. Schnatbaum†, J. Jansong†, J. Zerweck†, H. Wenschuh†, U.Reimer†, Ö. Türeci**** and U. Sahin* * BioNTech AG, Mainz, Germany ** Institute for Translational Oncology and Immunology (TRON), Mainz, Germany *** Department of Internal Medicine III, Experimental and Translational Oncology, Johannes Gutenberg-University, Mainz, Germany **** Ganymed Pharmaceuticals AG, Mainz, Germany † JPT Peptide Technologies, Volmerstrasse 5, 12489 Berlin, Germany The detection of therapeutic antibodies targeting membrane proteins in the course of (pre-)clinical development is often challenging due to the unavailability of the target molecule in its native form. As an alternative in this study, mimotopes for the antibody IMAB362 (Claudiximab) were discovered and optimized using phage display and peptide microarrays. The best mimotope was successfully used for the peptide ELISA- based quantification of IMAB362 in serum samples. The described process efficiently provides mimotopes for targets which are difficult to produce or handle. Introduction Three peptides (sequences 1a, 2a and 3a, Table 1) were selected IMAB362 (anti-Claudin 18.2) is a highly tumor-specific monoclonal for further analysis. IgG1 antibody currently in clinical development for the treatment Peptide microarrays represent a highly efficient approach for of advanced gastro-esophageal and stomach cancer [1, 2]. The peptide optimization because thousands of peptides can be antibody is directed against the cancer-specific cell surface target screened in parallel requiring only small amounts of precious Claudin 18 isoform 2 (CLDN18.2), a 27.7 kDa gastric differentiation analyte.
    [Show full text]
  • Identification of Mimotope Peptides Which Bind to the Mycotoxin
    APPLIED AND ENVIRONMENTAL MICROBIOLOGY, Aug. 1999, p. 3279–3286 Vol. 65, No. 8 0099-2240/99/$04.00ϩ0 Copyright © 1999, American Society for Microbiology. All Rights Reserved. Identification of Mimotope Peptides Which Bind to the Mycotoxin Deoxynivalenol-Specific Monoclonal Antibody QIAOPING YUAN,1† JAMES J. PESTKA,2 BRANDON M. HESPENHEIDE,3 3 2 1 LESLIE A. KUHN, JOHN E. LINZ, AND L. PATRICK HART * Departments of Botany and Plant Pathology,1 Food Science and Human Nutrition,3 and Biochemistry,2 Michigan State University, East Lansing, Michigan 48824 Received 23 October 1998/Accepted 6 May 1999 Monoclonal antibody 6F5 (mAb 6F5), which recognizes the mycotoxin deoxynivalenol (DON) (vomitoxin), was used to select for peptides that mimic the mycotoxin by employing a library of filamentous phages that have random 7-mer peptides on their surfaces. Two phage clones selected from the random peptide phage-displayed library coded for the amino acid sequences SWGPFPF and SWGPLPF. These clones were designated DON- PEP.2 and DONPEP.12, respectively. The results of a competitive enzyme-linked immunosorbent assay (ELISA) suggested that the two phage displayed peptides bound to mAb 6F5 specifically at the DON binding site. The amino acid sequence of DONPEP.2 plus a structurally flexible linker at the C terminus (SWGPF- PFGGGSC) was synthesized and tested to determine its ability to bind to mAb 6F5. This synthetic peptide (designated peptide C430) and DON competed with each other for mAb 6F5 binding. When translationally fused with bacterial alkaline phosphatase, DONPEP.2 bound specifically to mAb 6F5, while the fusion protein retained alkaline phosphatase activity.
    [Show full text]
  • Augmenting Anti-Tumor T Cell Responses to Mimotope Vaccination by Boosting with Native Tumor Antigens Jonathan D. Buhrman , Kimb
    Author Manuscript Published OnlineFirst on November 16, 2012; DOI: 10.1158/0008-5472.CAN-12-1005 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Augmenting Anti-Tumor T Cell Responses to Mimotope Vaccination by Boosting with Native Tumor Antigens Jonathan D. Buhrman1, Kimberly R. Jordan1, Lance U’Ren1, Jonathan Sprague1, Charles B. Kemmler1, and Jill E. Slansky1 1Integrated Department of Immunology, University of Colorado School of Medicine, Denver, CO Running title: Native antigen boost improves mimotope-elicited T cell response Keywords: mimotope, T cell, affinity, vaccine, altered-peptide ligands Financial support: This work was supported by ACS RSG-08-184-01-L1B and CA109560. JDB was supported by the Cancer Research Institute Pre-doctoral Emphasis Pathway in Tumor Immunology Fellowship. Conflict of Interest: The authors declare that there are no conflicts of interest Address correspondence to: Jill E. Slansky, Ph.D. Integrated Department of Immunology University of Colorado School of Medicine, National Jewish Health 1400 Jackson Street, Room K511 Denver, CO 80206 Phone: 303-398-1887 Fax: 303-398-1396 Email: [email protected] Word count: 5,198 (body text) Figures: 6 Tables: 1 Downloaded from cancerres.aacrjournals.org on September 25, 2021. © 2012 American Association for Cancer Research. Author Manuscript Published OnlineFirst on November 16, 2012; DOI: 10.1158/0008-5472.CAN-12-1005 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Abstract Vaccination with antigens expressed by tumors is one strategy for stimulating enhanced T cell responses against tumors. However, these peptide vaccines rarely result in efficient expansion of tumor-specific T cells or responses that protect against tumor growth.
    [Show full text]
  • Mimotope-Based Allergen-Specific Immunotherapy: Ready for Prime Time?
    www.nature.com/cmi Cellular & Molecular Immunology CORRESPONDENCE Mimotope-based allergen-specific immunotherapy: ready for prime time? Nicki Y. H. Leung1, Christine Y. Y. Wai1, Ka Hou Chu2 and Patrick S. C. Leung3 Cellular & Molecular Immunology (2019) 16:890–891; https://doi.org/10.1038/s41423-019-0272-7 INTRODUCTION and the safety and efficacy of mimotope-carrier constructs must Allergen-specific immunotherapy (AIT) is a therapeutic strategy to be evaluated case by case. restore the normal immune response by suppressing inflammatory effector cells and inducing regulatory cells specific to the culprit allergen. Conventionally, AIT is achieved by administering escalating RECENT ADVANCES IN MIMOTOPE-BASED AIT doses of allergen over a long treatment course. However, the use of Biopanning phage displayed5 or screening of one-bead-one- unmodified allergens for AIT often results in severe anaphylactic side compound combinatorial peptide libraries6 are high-throughput effects, and alternative approaches such as hypoallergens and T-cell approaches to identify mimotopes. Via screening of these peptide epitopes with enhanced safety have been considered. The use of libraries with allergen-specific IgE, the mimotopes obtained can be mimotopes in AIT is a relatively new concept, but earlier proof-of- subsequently mapped to the three-dimensional structure of the concept studies showed promising results for mimotopes, with allergen using bioinformatic algorithms to identify the particular decent safety profiles and immunomodulatory capacity1.Whilethe epitopes that they mimic. These methods are technically unde- treatment of cancer with mimotope-based immunotherapy has manding and cost effective. Many IgE epitopes of foods and already been tested in clinical trials2, mimotope-based AIT remains inhalant allergens have been identified using these approaches largely in the preclinical stage.
    [Show full text]
  • Epidermal Growth Factor Receptor Mimotope Alleviates Renal Fibrosis in Murine Unilateral Ureteral Obstruction Model
    Clinical Immunology 205 (2019) 57–64 Contents lists available at ScienceDirect Clinical Immunology journal homepage: www.elsevier.com/locate/yclim Epidermal growth factor receptor mimotope alleviates renal fibrosis in murine unilateral ureteral obstruction model T ⁎ Lin Yanga, Haoran Yuanb, Ying Yua, Nan Yua, Lilu Linga, Jianying Niua, , Yong Gua a Department of Nephrology, Shanghai Fifth People's Hospital, Fudan University, No. 801, Heqing Road, Shanghai 200240, PR China b Department of Central Laboratory, Shanghai Fifth People's Hospital, Fudan University, No. 801, Heqing Road, Shanghai 200240, PR China ARTICLE INFO ABSTRACT Keywords: Macrophages have been recognized as a vital factor that can promote renal fibrosis. Previously we reported that Epidermal growth factor receptor the EGFR mimotope could alleviate the macrophage infiltration in the Sjögren's syndrome-like animal model. In Macrophage current study, we sought to observe whether the active immunization induced by the EGFR mimotope could Mimotope ameliorate renal fibrosis in the murine Unilateral Ureteral Obstruction (UUO) model. A series of experiments Renal fibrosis showed the EGFR mimotope immunization could ameliorate renal fibrosis, reduce the expressions of fibronectin, CD9 α-SMA and collagen I and alleviate the infiltrations of F4/80+ macrophages in UUO model. Meanwhile, the EGFR mimotope immunization could inhibit the EGFR downstream signaling. Additionally, the frequency of and F4/80+CD9+/FAS+ macrophages significantly increased in spleen after the EGFR mimotope immunization. These evidence suggested that the EGFR mimotope could alleviate renal fibrosis by both inhibiting EGFR sig- naling and promoting macrophages apoptosis. 1. Introduction activation of renal fibroblasts independent of TGF-β expression or downstream signaling [8].
    [Show full text]
  • Oncogenic Protein Her-2/Neu Recognized by Trastuzumab on the Generation of Peptide Mimics of the Epitope
    Generation of Peptide Mimics of the Epitope Recognized by Trastuzumab on the Oncogenic Protein Her-2/neu This information is current as Angelika B. Riemer, Markus Klinger, Stefan Wagner, Astrid of September 24, 2021. Bernhaus, Luca Mazzucchelli, Hubert Pehamberger, Otto Scheiner, Christoph C. Zielinski and Erika Jensen-Jarolim J Immunol 2004; 173:394-401; ; doi: 10.4049/jimmunol.173.1.394 http://www.jimmunol.org/content/173/1/394 Downloaded from References This article cites 49 articles, 22 of which you can access for free at: http://www.jimmunol.org/content/173/1/394.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 24, 2021 *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 © 2004 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Generation of Peptide Mimics of the Epitope Recognized by Trastuzumab on the Oncogenic Protein Her-2/neu1 Angelika B. Riemer,*† Markus Klinger,‡ Stefan Wagner,*† Astrid Bernhaus,*† Luca Mazzucchelli,ʈ Hubert Pehamberger,*§ Otto Scheiner,*† Christoph C.
    [Show full text]
  • The Regulation of Peptide Mimotope/Epitope Recognition By
    The Regulation of Peptide Mimotope/Epitope Recognition by Monoclonal Antibodies by Richard Gary Smith B.Sc. (Hons) Thesis submitted to the University of Nottingham for the degree of Doctor of Philosophy, March 2002. TABLE OF CONTENTS Abstract………………………………………………………………...……….…….8 Acknowledgements…………………………………………………………………...9 Glossary of terms……………………………………………………………………10 Chapter 1 Antibody Purification…………………………………………………..11 1.1 Introduction ......................................................................................................11 1.1.1 Antibodies ................................................................................................11 1.1.2 Monoclonal and engineered Antibodies...................................................12 1.2 Examples of a therapeutic and a commercially applied monoclonal antibody17 1.2.1 C595 monoclonal antibody (NCRC48)...................................................17 1.2.2 mAb 4155.................................................................................................18 1.3 Approaches to antibody purification................................................................20 1.3.1 Column chromatography..........................................................................20 1.3.2 Fluidized bed and expanded bed adsorption ............................................20 1.3.3 High performance Tangential Flow Filtration (HPTFF)..........................21 1.3.4 Magnetic beads.........................................................................................21 1.4 Physical
    [Show full text]
  • T-Cell Responses Induced by Beryllium Exposure in HLA-DP2 Transgenic Mice
    ARTICLES nature publishing group Metal-specific CD4 þ T-cell responses induced by beryllium exposure in HLA-DP2 transgenic mice MT Falta1, AN Tinega1, DG Mack1, NA Bowerman1, F Crawford2,3, JW Kappler2,3, C Pinilla4 and AP Fontenot1,2 Chronic beryllium disease (CBD) is a granulomatous lung disorder that is associated with the accumulation of beryllium (Be)-specific CD4 þ T cells into the lung. Genetic susceptibility is linked to HLA-DPB1 alleles that possess a glutamic acid at position 69 (bGlu69), and HLA-DPB1*02:01 is the most prevalent bGlu69-containing allele. Using HLA-DP2 transgenic (Tg) mice, we developed a model of CBD that replicates the major features of the human disease. Here we characterized the T-cell receptor (TCR) repertoire of Be-responsive CD4 þ T cells derived from the lungs of Be oxide–exposed HLA-DP2 Tg mice. The majority of Be-specific T-cell hybridomas expressed TCR Vb6, and a subset of these hybridomas expressed identical or nearly identical b-chains that were paired with different a-chains. We delineated mimotopes that bind to HLA-DP2 and form a complex recognized by Be-specific CD4 þ T cells in the absence of Be. These Be-independent peptides possess an arginine at p5 and a tryptophan at p7 that surround the Be-binding site within the HLA-DP2 acidic pocket and likely induce charge and conformational changes that mimic those induced by the Be2 þ cation. Collectively, these data highlight the interplay between peptides and Be in the generation of an adaptive immune response in metal-induced hypersensitivity.
    [Show full text]
  • K-Ras Peptide Mimotope Induces Antigen Specific Th1 and B-Cell Immune Responses Against G12A-Mutated K-Ras Antigen in Balb/C
    Article K-Ras Peptide Mimotope Induces Antigen Specific Th1 and B-Cell Immune Responses against G12A-Mutated K-Ras Antigen in Balb/c Mice Pui Yan Siak 1, Kuan Yee Wong 1, Adelene Ai-Lian Song 2 , Raha Abdul Rahim 3 and Lionel Lian Aun In 1,* 1 Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Kuala Lumpur 56000, Malaysia; [email protected] (P.Y.S.); [email protected] (K.Y.W.) 2 Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia, Selangor 43400, Malaysia; [email protected] 3 Technical University of Malaysia Malacca, Malacca 76100, Malaysia; [email protected] * Correspondence: [email protected]; Tel.: +603-91-01-88-80 Abstract: KRAS G12A somatic point mutation in adenocarcinomas is categorized clinically as inel- igibility criteria for anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies. In this study, a modified G12A-K-ras epitope (139A) with sequence-specific modifications to im- prove immunogenicity was developed as a potential vaccine against G12A-mutant KRAS cancers. Additionally, coupling of the 139A epitope with a tetanus toxoid (TTD) universal T-cell epitope to improve antigenicity was also reported. To facilitate convenient oral administration, Lactococcus lactis, which possesses innate immunomodulatory properties, was chosen as a live gastrointestinal delivery L. lactis vehicle. Recombinant strains secreting a G12A mutated K-ras control and 139A with and without TTD fusion were generated for comparative immunogenicity assessment. BALB/c mice were Citation: Siak, P.Y.; Wong, K.Y.; Song, immunized orally, and high survivability of L. lactis passage through the gastrointestinal tract was A.A.-L.; Rahim, R.A.; In, L.L.A.
    [Show full text]
  • A Rationally Designed Mimotope Library for Profiling of the Human Igm Repertoire
    bioRxiv preprint doi: https://doi.org/10.1101/308973; this version posted December 10, 2018. 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 A rationally designed mimotope library for profiling of the human IgM repertoire 2 3 4 Anastas Pashov1, *, Velizar Shivarov2, Maya Hadzhieva1, Victor Kostov1,3, Dilyan Ferdinandov3, Karen- 5 Marie Heinz5, Shina Pashova1,4, Milena Todorova1, Tchavdar Vassilev1, Thomas Kieber-Emmons6, 6 Leonardo A. Meza-Zepeda5, Eivind Hovig5 7 8 1 Department of Immunology, Stephan Angeloff Institute of Microbiology, BAS, Sofia, Bulgaria 9 2 Laboratory of Clinical Immunology and Department of Clinical Hematology, Sofiamed University 10 Hospital, Sofia, Bulgaria; ORCID: 0000-0001-5362-7999 11 3 Neurosurgery Clinic, St. Ivan Rilsky Hospital, MU, Sofia, Bulgaria 12 4 Department of Molecular Immunology, Institute of Biology and Immunology of Reproduction, BAS, 13 Sofia, Bulgaria 14 5 Department of Tumor Immunology, Oslo University Hospital, Oslo, Norway 15 6 Winthrop P. Rockefeller Cancer Research Center, UAMS, Little Rock, AR, USA 16 17 18 *Corresponding author. 19 Mailing Address: 20 Institute of Microbiology, BAS, 21 Acad. G Bonchev St, block 26 22 Sofia 1113, Bulgaria 23 E-mail: [email protected] (AP) 24 Phone: +359 897 944628 25 26 27 28 29 Running title: A rationally designed mimotope library for IgM igome studies 30 31 1 bioRxiv preprint doi: https://doi.org/10.1101/308973; this version posted December 10, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.
    [Show full text]
  • Regulatory Vs. Inflammatory Cytokine T-Cell Responses to Mutated Insulin Peptides in Healthy and Type 1 Diabetic Subjects
    Regulatory vs. inflammatory cytokine T-cell responses to mutated insulin peptides in healthy and type 1 diabetic subjects Maki Nakayamaa,b, Kristen McDaniela, Lisa Fitzgerald-Millera, Carol Kiekhaefera, Janet K. Snell-Bergeona, Howard W. Davidsona,b, Marian Rewersa, Liping Yua, Peter Gottlieba, John W. Kapplerb,c,d,1, and Aaron Michelsa,1 aBarbara Davis Center for Childhood Diabetes, bDepartment of Immunology and Microbiology, and dProgram in Structural Biology and Biophysics, University of Colorado School of Medicine, Aurora, CO 80045; and cDepartment of Biomedical Research, Howard Hughes Medical Institute, National Jewish Health, Denver, CO 80206 Contributed by John W. Kappler, February 13, 2015 (sent for review October 10, 2014; reviewed by Mark Peakman and Jay Skyler) Certain class II MHC (MHCII) alleles in mice and humans confer risk in the IAg7 β-chain at position 57 changing the conserved Asp(D) for or protection from type 1 diabetes (T1D). Insulin is a major au- to Ser(S) favors the binding of peptides that place an acidic toantigen in T1D, but how its peptides are presented to CD4 T cells amino acid at the p9 position in the peptide binding groove. In by MHCII risk alleles has been controversial. In the mouse model Reg3, the B22 Arg(R) of B:9–23 is a very poor match for this of T1D, CD4 T cells respond to insulin B-chain peptide (B:9–23) pocket, but mutating the R to Glu(E) creates an insulin mimo- mimotopes engineered to bind the mouse MHCII molecule, IAg7,in tope peptide (B22E) that binds to IAg7 almost exclusively in an unfavorable position or register.
    [Show full text]
  • Screening and Identification of Mimotopes of the Major Shrimp Allergen Tropomyosin Using One-Bead-One-Compound Peptide Libraries
    Cellular & Molecular Immunology (2017) 14, 308–318 ß 2017 CSI and USTC. All rights reserved 1672-7681/17 $32.00 www.nature.com/cmi RESEARCH ARTICLE Screening and identification of mimotopes of the major shrimp allergen tropomyosin using one-bead-one- compound peptide libraries Nicki YH Leung1, Christine YY Wai1, Marco HK Ho2, Ruiwu Liu3, Kit S Lam3, Jin Jun Wang4, Shang An Shu4, Ka Hou Chu1 and Patrick SC Leung4 The one-bead-one-compound (OBOC) combinatorial peptide library is a powerful tool to identify ligand and receptor interactions. Here, we applied the OBOC library technology to identify mimotopes specific to the immunoglobulin E (IgE) epitopes of the major shellfish allergen tropomyosin. OBOC peptide libraries with 8–12 amino acid residues were screened with serum samples from patients with shellfish allergy for IgE mimotopes of tropomyosin. Twenty-five mimotopes were identified from the screening and their binding reactivity to tropomyosin-specific IgE was confirmed by peptide ELISA. These mimotopes could be divided into seven clusters based on sequence homology, and epitope mapping by EpiSearch of the clustered mimotopes was performed to characterize and confirm the validity of mimotopes. Five out of six of the predicted epitopes were found to overlap with previously identified epitopes of tropomyosin. To further confirm the mimicry potential of mimotopes, BALB/c mice were immunized with mimotopes conjugated to keyhole limpet hemocyanin and assayed for their capacity to induce tropomyosin-specific antibodies. BALB/c mice that received mimotope immunization were found to have an elevated level of tropomyosin-specific immunoglobulin G, but not mice that received an irrelevant mimotope.
    [Show full text]