DOCSLIB.ORG

X-Ray Crystallography Respiratory Allergen Phl P 2 As Revealed by Conformational Epitope of the Major High-Affinity Ige Recognit

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
X-Ray Crystallography Respiratory Allergen Phl P 2 As Revealed by Conformational Epitope of the Major High-Affinity Ige Recognit High-Affinity IgE Recognition of a Conformational Epitope of the Major Respiratory Allergen Phl p 2 As Revealed by X-Ray Crystallography This information is current as of September 28, 2021. Sivaraman Padavattan, Sabine Flicker, Tilman Schirmer, Christoph Madritsch, Stefanie Randow, Gerald Reese, Stefan Vieths, Christian Lupinek, Christof Ebner, Rudolf Valenta and Zora Markovic-Housley J Immunol 2009; 182:2141-2151; ; Downloaded from doi: 10.4049/jimmunol.0803018 http://www.jimmunol.org/content/182/4/2141 http://www.jimmunol.org/ References This article cites 62 articles, 12 of which you can access for free at: http://www.jimmunol.org/content/182/4/2141.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 © 2009 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology High-Affinity IgE Recognition of a Conformational Epitope of the Major Respiratory Allergen Phlp2AsRevealed by X-Ray Crystallography1 Sivaraman Padavattan,2* Sabine Flicker,2† Tilman Schirmer,* Christoph Madritsch,† Stefanie Randow,‡ Gerald Reese,‡ Stefan Vieths,‡ Christian Lupinek,† Christof Ebner,§ Rudolf Valenta,3,4†¶ and Zora Markovic-Housley3* We report the three-dimensional structure of the complex between the major respiratory grass pollen allergen Phl p 2 and its specific human IgE-derived Fab. The Phl p 2-specific human IgE Fab has been isolated from a combinatorial library constructed from lymphocytes of a pollen allergic patient. When the variable domains of the IgE Fab were grafted onto human IgG1, the resulting Ab (huMab2) inhibited strongly the binding of allergic patients’ IgE to Phlp2aswell as allergen-induced basophil Downloaded from degranulation. Analysis of the binding of the allergen to the Ab by surface plasmon resonance yielded a very low dissociation ؋ ؊10 ␧ ؍ constant (KD 1.1 10 M), which is similar to that between IgE and Fc RI. The structure of the Phl p 2/IgE Fab complex was determined by x-ray crystallography to 1.9 Å resolution revealing a conformational epitope (876 Å2) comprised of the planar surface of the four-stranded anti-parallel ␤-sheet of Phl p 2. The IgE-defined dominant epitope is discontinuous and formed by 21 residues located mostly within the ␤ strands. Of the 21 residues, 9 interact directly with 5 of the 6 CDRs (L1, L3, H1, H2, H3) of the IgE Fab predominantly by hydrogen bonding and van der Waals interactions. Our results indicate that IgE Abs recognize http://www.jimmunol.org/ conformational epitopes with high affinity and provide a structural basis for the highly efficient effector cell activation by allergen/ IgE immune complexes. The Journal of Immunology, 2009, 182: 2141–2151. he hallmark of type I hypersensitivity diseases, e.g., al- series of inflammatory processes through the binding to and cross- lergic asthma, rhinitis, skin inflammation, food allergy, linking of the high-affinity receptor for IgE (Fc␧RI) on mast cells, T anaphylactic shock, which affect more than 25% of the basophils, eosinophils, and professional APCs such as dendritic population, is the formation of IgE Abs against per se harmless cells (4–7). In contrast, IgE-allergen immune complexes can reg- Ags, i.e., allergens (1). IgE Abs represent the least abundant class ulate IgE production and T cell activation via the low-affinity re- by guest on September 28, 2021 of immunoglobulins occurring at approximately 1000-fold lower ceptor for IgE (Fc␧RII, i.e., CD23) (8–11). Allergen recognition concentrations in serum and other body fluids compared with IgG also directly stimulates the IgE production in IgEϩ B cells leading and other Ig classes (2, 3). Nevertheless, minute amounts of im- to increased levels of serum IgE in patients after allergen contact mune complexes consisting of IgE Abs and allergens can trigger a (12, 13). Interestingly, mucosal contact with tiny allergen amounts *Division of Structural Biology, Biozentrum, University of Basel, Basel, Switzerland; strongly boosts allergen-specific IgE Ab production but only †Division of Immunopathology, Department of Pathophysiology, Center for Physi- weakly induces rises of allergen-specific IgG or IgA production ology and Pathophysiology, Medical University of Vienna, Vienna, Austria; ‡Paul Ehrlich Institut, Department of Allergology, Langen, Germany; §Allergie-Ambulato- (13). rium Reumannplatz, Vienna, Austria; ¶Christian Doppler Laboratory for Allergy Re- Moreover, extremely low concentrations (ng/ml) of allergens search, Department of Pathophysiology, Center for Physiology and Pathophysiology, are sufficient to induce rapid and strong inflammatory responses Medical University of Vienna, 1090 Vienna, Austria through degranulation of mast cells and basophils as well as Received for publication September 12, 2008. Accepted for publication November 28, 2008. through the activation of allergen-specific T cells (6, 14, 15). One The costs of publication of this article were defrayed in part by the payment of page prerequisite for this efficient activation of immune cells is a high- charges. This article must therefore be hereby marked advertisement in accordance affinity binding of allergen-IgE immune complexes to Fc␧RI on with 18 U.S.C. Section 1734 solely to indicate this fact. effector cells. In fact, IgE binds primarily with its C␧2 domain with 1 This project was supported by the Swiss National Foundation Grant 31-116804 (to extremely high affinity (K ϳ 10Ϫ9 M) to the ␣-chain of Fc␧RI Z.M.-H.), by Grant 813003 of the Austrian Research Promotion Agency and BIOMAY, D Vienna, Austria to (S.F.), by Grant F1815 of the Austrian Science Fund (to R.V.), by a (16). research grant from BIOMAY, Vienna, Austria, and the Christian Doppler Research Blood and body fluids of allergic patients contain relatively high Association, Vienna, Austria. levels of allergen-specific IgG Abs (17). However, only after a Coordinates and structure factors have been deposited in the Protein Data Bank with more than 100-fold increase of allergen-specific IgG during aller- accession numbers 2vxq and r2vxqsf, respectively. gen-specific immune therapy are these IgG Abs able to compete 2 S.P. and S.F. contributed equally to this study. with allergen-specific IgE Abs and to prevent mast cell degran- 3 R.V. and Z.M.-H. contributed equally to this study. ulation and T cell activation (18). One possibility for the effi- 4 Address correspondence and reprint requests to Prof. Rudolf Valenta, Christian cient recognition of allergen by IgE Abs is that IgE recognizes Doppler Laboratory for Allergy Research, Division of Immunopathology, Department of Pathophysiology, Center for Physiology and Pathophysiology, Vienna General different epitopes on allergens than IgG Abs. Evidence for dif- Hospital, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, ferent epitope recognition comes from epitope mapping studies Austria. E-mail: [email protected] performed with allergen fragments and the analysis of the bind- Copyright © 2009 by The American Association of Immunologists, Inc. 0022-1767/09/$2.00 ing specificities of defined allergen-specific human IgG Abs www.jimmunol.org/cgi/doi/10.4049/jimmunol.0803018 2142 X-RAY CRYSTAL STRUCTURE OF AN ALLERGEN/IgE COMPLEX 0.3nM 40 0.6nM 1.25nM 2.5nM 5.0nM FIGURE 1. Sensor chip-based 10nM studies of the interaction between rPhl 30 20nM p 2 and huMab2. rPhl p 2 was injected at 2-fold increasing concentrations from 0.3 to 20 nM (curves bottom to 20 top) into the flow cell containing im- mobilized huMab2 rPhl p 2-specific RU Ab. Recorded curves (colored) and 10 calculated curves (black), which repre- sent a fitting of the response data to a 1:1 interaction model were superim- 0 posed onto each other. The signal inten- sity (RU) is shown on the y-axis whereas the x-axis displays the time (s). -10 0 500 1000 1500 2000 2500 Time [s] Downloaded from (19, 20). Studies performed with allergen-specific serum IgE vs Determination of the affinity and kinetics of the interaction serum IgG report controversial results regarding possible between rPhl p 2 and huMab2 differences between the binding strength of allergen-specific The surface of a CM5 sensor chip (BIACore AB) was activated by the injec- http://www.jimmunol.org/ IgE and IgG Abs (21, 22). tion of a 1:1 mixture of EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Many three-dimensional structures of important allergens have hydrochloride) and NHS at a flow rate of 5 ␮l/min for 7 min. The purified been solved but only few allergen-Ab complexes have been char- huMab2 (c ϭ 10 ␮g/ml) which had been diluted in 10 mM sodium acetate (pH acterized so far (23–26). We have previously isolated human IgE Fabs specific for major respiratory grass pollen allergens from a Table I. Inhibition of patients’ IgE binding to rPhlp2bytherPhl p combinatorial library constructed from lymphocytes of a pollen a allergic patient (27–29). 2-specific antibodies This is the first report of the three-dimensional structure of the ␣ ␣ Phlp5 huMab2 % r Phl p r Phl p % by guest on September 28, 2021 complex between an IgE-derived Fab with a major respiratory al- Patient ab (OD) (OD) Inhibition 5 (OD) 2 (OD) Inhibition lergen, the grass pollen allergen Phl p 2, which is recognized by 1 1.510 0.634 58.0 n.d.
Load more

Recommended publications
  • Evaluation of T-Cell and B-Cell Epitopes and Design of Multivalent Vaccines Against Htlv-1 Diseases
    EVALUATION OF T-CELL AND B-CELL EPITOPES AND DESIGN OF MULTIVALENT VACCINES AGAINST HTLV-1 DISEASES DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Roshni Sundaram, M.S. * * * * * The Ohio State University 2003 Dissertation Committee: Approved by Professor Pravin T.P. Kaumaya, Adviser Professor Christopher M. Walker Adviser Professor Neil R. Baker Department of Microbiology Professor Marshall V. Williams ABSTRACT Human T-cell lymphotropic virus type I (HTLV-1) is a C type retrovirus that is the causative agent of an aggressive T-cell malignancy, adult T-cell leukemia/lymphoma (ATLL). The virus is also implicated in a number of inflammatory disorders, the most prominent among them being HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP). HTLV-1, like many viruses that cause chronic infection, has adapted to persist in the face of an active immune response in infected individuals. The viral transactivator Tax is the primary target of the cellular immune response and humoral responses are mainly directed against the envelope protein. Vaccination against HTLV-1 is a feasible option as there is very little genetic and antigenic variability. Vaccination regimes against chronic viruses must be aimed at augmenting the immune response to a level that is sufficient to clear the virus. This requires that the vaccine delivers a potent stimulus to the immune system that closely resembles natural infection to activate both the humoral arm and the cellular arm. It is also clear that multicomponent vaccines may be more beneficial in terms of increasing the breadth of the immune response as well as being applicable in an outbred population.
    [Show full text]
  • Mapping B-Cell Epitopes for Nonspecific Lipid Transfer Proteins of Legumes Consumed in India and Identification of Critical Resi
    foods Article Mapping B-Cell Epitopes for Nonspecific Lipid Transfer Proteins of Legumes Consumed in India and Identification of Critical Residues Responsible for IgE Binding Ankita Mishra 1,* and Ashok Kumar 1,2,3,4 1 Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur 208016, UP, India; [email protected] 2 Centre for Environmental Science and Engineering, Indian Institute of Technology Kanpur, Kanpur 208016, UP, India 3 Centre for Nanosciences, Indian Institute of Technology Kanpur, Kanpur 208016, UP, India 4 The Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur, Kanpur 208016, UP, India * Correspondence: [email protected] Abstract: Nonspecific lipid transfer proteins (nsLTPs) have been categorized as panallergens and display widespread occurrence across plant-kingdom. Present study, investigated B-cell epitopes for LTPs from chickpea, mung-bean, cowpea, pigeon-pea, and soybean via in silico methods. In-silico predicted regions were evaluated for epitope-conservancy and property-based peptide similarity search by different allergen databases. Additionally, the in-silico predicted regions were compared Citation: Mishra, A.; Kumar, A. with the experimentally validated epitopes of peach-LTP. Sequence-homology studies showed that Mapping B-Cell Epitopes for chickpea and mung-bean LTPs shared significant homology, i.e., >70% and >60%, respectively, with Nonspecific Lipid Transfer Proteins of other LTP allergens from lentil, garden-pea, peanut, etc. Phylogenetic-analysis also showed chickpea Legumes Consumed in India and and mung-bean LTPs to be closely related to allergenic LTPs from lentil and peanut, respectively. Identification of Critical Residues Responsible for IgE Binding. Foods Epitope-conservation analysis showed that two of the predicted B-cell epitopic regions in chickpea 2021, 10, 1269.
    [Show full text]
  • Opportunities for Conformation-Selective Antibodies in Amyloid-Related Diseases
    Antibodies 2015, 4, 170-196; doi:10.3390/antib4030170 OPEN ACCESS antibodies ISSN 2073-4468 www.mdpi.com/journal/antibodies Review Opportunities for Conformation-Selective Antibodies in Amyloid-Related Diseases Marta Westwood * and Alastair D. G. Lawson Structural Biology, UCB, 216 Bath Road, Slough, SL1 3WE UK; E-Mail: [email protected]. * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +44-1-753-534-655 (ext.7749); Fax: +44-1-753-536-632. Academic Editor: Dimiter S. Dimitrov Received: 13 May 2015 / Accepted: 9 July 2015 / Published: 15 July 2015 Abstract: Assembly of misfolded proteins into fibrillar deposits is a common feature of many neurodegenerative diseases. Developing effective therapies to these complex, and not yet fully understood diseases is currently one of the greatest medical challenges facing society. Slow and initially asymptomatic onset of neurodegenerative disorders requires profound understanding of the processes occurring at early stages of the disease including identification and structural characterisation of initial toxic species underlying neurodegeneration. In this review, we chart the latest progress made towards understanding the multifactorial process leading to amyloid formation and highlight efforts made in the development of therapeutic antibodies for the treatment of amyloid-based disorders. The specificity and selectivity of conformational antibodies make them attractive research probes to differentiate between transient states preceding formation of mature fibrils and enable strategies for potential therapeutic intervention to be considered. Keywords: antibody; amyloids; conformation; prion; Alzheimer’s; Parkinson’s; fibrils, tau; Huntingtin; protein misfolding 1. Introduction Correct protein folding is crucial for maintaining healthy biological functions.
    [Show full text]
  • Inhibition of Allergic Reactivity Through Targeting Fcεri-Bound Ige with Humanized Low-Affinity Antibodies
    Inhibition of Allergic Reactivity through Targeting Fc εRI-Bound IgE with Humanized Low-Affinity Antibodies This information is current as Ke Zhang, Michael Elias, Hong Zhang, Jeffrey Liu, of September 27, 2021. Christopher Kepley, Yun Bai, Dean D. Metcalfe, Zachary Schiller, Yang Wang and Andrew Saxon J Immunol published online 21 October 2019 http://www.jimmunol.org/content/early/2019/10/19/jimmun ol.1900112 Downloaded from Why The JI? Submit online. http://www.jimmunol.org/ • 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 *average by guest on September 27, 2021 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 © 2019 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published October 21, 2019, doi:10.4049/jimmunol.1900112 The Journal of Immunology Inhibition of Allergic Reactivity through Targeting Fc«RI-Bound IgE with Humanized Low-Affinity Antibodies Ke Zhang,* Michael Elias,† Hong Zhang,* Jeffrey Liu,* Christopher Kepley,† Yun Bai,‡ Dean D. Metcalfe,‡ Zachary Schiller,x Yang Wang,x and Andrew Saxon* Options for effective prevention and treatment of epidemic allergic diseases remain limited, and particularly so for IgE-mediated 26 28 food allergies.
    [Show full text]
  • Ige – the Main Player of Food Allergy
    DDMOD-431; No of Pages 8 Vol. xxx, No. xx 2016 Drug Discovery Today: Disease Models Editors-in-Chief Jan Tornell – AstraZeneca, Sweden DRUG DISCOVERY Andrew McCulloch – University of California, SanDiego, USA TODAY DISEASE MODELS IgE – the main player of food allergy 1 2,3 2 Henrike C.H. Broekman , Thomas Eiwegger , Julia Upton , 4, Katrine L. Bøgh * 1 Department of Dermatology/Allergology, University Medical Centre Utrecht (UMCU), Utrecht, The Netherlands 2 Division of Immunology and Allergy, Food Allergy and Anaphylaxis Program, The Department of Paediatrics, Hospital for Sick Children, Toronto, Canada 3 Research Institute, Physiology and Experimental Medicine, The University of Toronto, Toronto, Canada 4 National Food Institute, Technical University of Denmark, Søborg, Denmark Food allergy is a growing problem worldwide, presently Section editor: affecting 2–4% of adults and 5–8% of young children. IgE Michelle Epstein – Medical University of Vienna, is a key player in food allergy. Consequently huge Department of Dermatology, DIAID, Experimental Allergy, Waehringer Guertel 18-20, Room 4P9.02, A1090, efforts have been made to develop tests to detect Vienna, Austria. either the presence of IgE molecules, their allergen binding sites or their functionality, in order to provide allergen ingestion [1], and involve one or more of the follow- information regarding the patient’s food allergy. The ing systems; the skin (pruritus, urticaria, or angioedema), the ultimate goal is to develop tools that are capable of gastro-intestinal tract (diarrhea, vomiting, contractions, in- creased bowel movement), the respiratory tract (asthma at- discriminating between asymptomatic sensitization tack, hoarseness, stridor/laryngeal angioedema) or the and a clinically relevant food allergy, and between cardiovascular system (dizziness, drop in blood pressure, loss different allergic phenotypes in an accurate and trust- of consciousness) [2,3].
    [Show full text]
  • Characterization of Conformational B-Cell
    PEPTIDE-BASED B-CELL EPITOPE VACCINES TARGETING HER-2/NEU DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in the Graduate School of The Ohio State University By Joan T. Garrett, B.S./B.A. ***** The Ohio State University 2007 Dissertation Committee: Approved by Professor Pravin Kaumaya, Advisor ___________________________ Advisor Professor Dehua Pei, Advisor Professor Ross Dalbey ___________________________ Advisor Professor Thomas Magliery Graduate Program in Chemistry ABSTRACT HER-2/neu (ErbB2), a member of the epidermal growth factor family of receptors (EGFR) is overexpressed in a significant fraction of breast cancers. It is an attractive target for receptor-directed antitumor therapy using monoclonal antibodies. Trastuzumab and pertuzumab are growth-inhibitory humanized antibodies targeting the oncogenic protein HER-2/neu. Although passive immunotherapy with trastuzumab is approved for treatment of breast cancer, a number of concerns exist with passive immunotherapy. Treatment is expensive, and has a limited duration of action, necessitating repeated administrations of the monoclonal antibody. Active immunotherapy with conformational B-cell epitopes affords the possibility of generating an enduring immune response, eliciting protein-reactive high-affinity anti-peptide antibodies. The three-dimensional structure of human HER-2 in complex with trastuzumab reveals that the antigen binding region of HER-2 spans residues 563-626 that comprises an extensive disulfide bonding pattern. In order to minimally dissect the interacting binding region of HER-2, we have designed four synthetic peptides with different levels of conformational flexibility. Chimeric peptides incorporating the measles virus fusion ‘promiscuous’ T cell epitope via a four-residue linker sequence were synthesized, purified, and characterized.
    [Show full text]
  • HDX-MS for Epitope Characterization of a Therapeutic ANTIBODY Candidate on the Calcium-Binding Protein Annexin-A1
    antibodies Article HDX-MS for Epitope Characterization of a Therapeutic ANTIBODY Candidate on the Calcium-Binding Protein Annexin-A1 Marius Gramlich 1, Henry C. W. Hays 2, Scott Crichton 2, Philipp D. Kaiser 1, Anne Heine 1, Nicole Schneiderhan-Marra 1, Ulrich Rothbauer 1,3, Dieter Stoll 1,4, Sandra Maier 1 and Anne Zeck 1,* 1 NMI, Natural and Medical Sciences Institute at the University of Tuebingen, Markwiesenstr. 55, 72770 Reutlingen, Germany; [email protected] (M.G.); [email protected] (P.D.K.); [email protected] (A.H.); [email protected] (N.S.-M.); [email protected] (U.R.); [email protected] (D.S.); [email protected] (S.M.) 2 Medannex Ltd., 1 Lochrin Square, Fountainbridge, Edinburgh EH3 9QA, UK; [email protected] (H.C.W.H.); [email protected] (S.C.) 3 Pharmaceutical Biotechnology, Eberhard Karls University Tuebingen, Geschwister-Scholl-Platz, 72074 Tuebingen, Germany 4 Department of Life Sciences, University of Applied Sciences Albstadt-Sigmaringen, Anton-Guentherstr. 51, 72488 Sigmaringen, Germany * Correspondence: [email protected]; Tel.: +49-7121-51530-0; Fax: +49-7121-51530-816 Abstract: Annexin-A1 (ANXA1) belongs to a class of highly homologous Ca2+-dependent phospholipid- binding proteins. Its structure consists of a core region composed of four homologous repeats ar- ranged in a compact, hydrolysis-resistant structure and an N-terminal region with a Ca2+-dependent conformation. ANXA1 is involved in several processes, including cell proliferation, apoptosis, Citation: Gramlich, M.; Hays, metastasis, and the inflammatory response. Therefore, the development of antibodies blocking H.C.W.; Crichton, S.; Kaiser, P.D.; selected regions on ANXA1 holds great potential for the development of novel therapeutics treating Heine, A.; Schneiderhan-Marra, N.; inflammatory and cancer diseases.
    [Show full text]
  • Epitope Recognition in HLA-DR3 Transgenic Mice Immunized to TSH-R Protein Or Peptides Hidefumi Inaba
    University of Rhode Island DigitalCommons@URI Institute for Immunology and Informatics Faculty Institute for Immunology and Informatics (iCubed) Publications 2013 Epitope Recognition in HLA-DR3 Transgenic Mice Immunized to TSH-R Protein or Peptides Hidefumi Inaba Leonard Moise University of Rhode Island See next page for additional authors Follow this and additional works at: https://digitalcommons.uri.edu/immunology_facpubs The University of Rhode Island Faculty have made this article openly available. Please let us know how Open Access to this research benefits oy u. This is a pre-publication author manuscript of the final, published article. Terms of Use This article is made available under the terms and conditions applicable towards Open Access Policy Articles, as set forth in our Terms of Use. Citation/Publisher Attribution Inaba, H., Moise, L., Martin, W., De Groot, A. S., Desrosiers, J., Tassone, R., Buchman, G., Akamizu, T., & De Groot, L. J. (2013). Epitope Recognition in HLA-DR3 Transgenic Mice Immunized to TSH-R Protein or Peptides. Endocrinology, 154(6), 2234-2243. Available at: http://dx.doi.org/10.1210/en.2013-1033 This Article is brought to you for free and open access by the Institute for Immunology and Informatics (iCubed) at DigitalCommons@URI. It has been accepted for inclusion in Institute for Immunology and Informatics Faculty Publications by an authorized administrator of DigitalCommons@URI. For more information, please contact [email protected]. Authors Hidefumi Inaba, Leonard Moise, William Martin, Anne S. De Groot, Joe Desrosiers, Ryan Tassone, George Buchman, Takashi Akamizu, and Leslie J. De Groot This article is available at DigitalCommons@URI: https://digitalcommons.uri.edu/immunology_facpubs/68 1 Title 2 EPITOPE RECOGNITION IN HLA-DR3 TRANSGENIC MICE IMMUNIZED TO TSH-R 3 PROTEIN OR PEPTIDES 4 5 Hidefumi Inaba, Leonard Moise, William Martin, Anne S.earls De Groot, 6 Joe Desrosiers, Ryan Tassone, George Buchman, Takashi Akamizu, 7 and Leslie J.
    [Show full text]
  • Recognition Stereotyped Repertoire of Epitope Bind the Same Linear Peptide
    Two Human Neonatal IgM Antibodies Encoded by Different Variable-Region Genes Bind the Same Linear Peptide: Evidence for a Stereotyped Repertoire of Epitope Recognition1 Bradley T. Messmer,* James J. Sullivan,* Nicholas Chiorazzi,† Toby C. Rodman,* and David S. Thaler2* Two monoclonal IgM Abs have been produced from lymphocytes isolated from two human umbilical cord bloods. These mAbs recognize a conformational epitope present in a CNBr digestion fraction of lactoferrin. Linear epitopes recognized by each mAb were selected from several phage display peptide libraries. In each case, phages displaying a peptide with a motif defined by [WF],G,[EQS],N were recovered. Phages displaying that motif bound equally well to either mAb but did not bind to control IgM. A peptide bearing this motif competed with the phage-displayed peptides for binding to either mAb. The same peptide also competes with a component of the CNBr digestion fraction of lactoferrin for Ab binding in ELISA. The Abs use different families of VH,JH, and VK gene cassettes but use the same JK cassette. All segments are virtually identical to their germline gene counterparts. This work provides further evidence that certain innate specificities are stereotyped among individuals. The Jour- nal of Immunology, 1999, 162: 2184–2192. uman serum contains Abs that have not arisen as a result Several lines of evidence support the possibility that the natu- of direct immunization with foreign Ag or pathogenic rally occurring Ab repertoire in human neonates contains certain H exposure (1). These Abs have been called “natural” (2) stereotyped specificities. Homogenous tissue extracts separated on or “innate” (3).
    [Show full text]
  • Structure of a Protective Epitope of Group B Streptococcus Type III Capsular Polysaccharide
    Structure of a protective epitope of group B Streptococcus type III capsular polysaccharide Filippo Carbonia, Roberto Adamoa,1, Monica Fabbrinia, Riccardo De Riccoa, Vittorio Cattaneoa, Barbara Brogionia, Daniele Veggia, Vittoria Pintoa, Irene Passalacquaa, Davide Oldrinia, Rino Rappuolia,2, Enrico Malitoa, Immaculada y Ros Margarita,1, and Francesco Bertia,1,2 aGSK Vaccines, 53100 Siena, Italy Contributed by Rino Rappuoli, March 27, 2017 (sent for review February 3, 2017; reviewed by Dennis L. Kasper and Robert J. Woods) Despite substantial progress in the prevention of group B Strepto- GBS is an encapsulated Gram-positive β-hemolytic pathogen coccus (GBS) disease with the introduction of intrapartum antibiotic causing neonatal sepsis and meningitis, particularly in infants born prophylaxis, this pathogen remains a leading cause of neonatal to mothers carrying the bacteria (12). The GBS capsular PS is infection. Capsular polysaccharide conjugate vaccines have been constituted by multiple RUs (from ∼50 up to 300 per polymer) of tested in phase I/II clinical studies, showing promise for further de- four to seven monosaccharides shaped to form a backbone and one velopment. Mapping of epitopes recognized by protective anti- or two side chains. Ten serotypes presenting a unique pattern of bodies is crucial for understanding the mechanism of action of glycosidic linkages have been identified and their primary struc- vaccines and for enabling antigen design. In this study, we report β the structure of the epitope recognized by a monoclonal antibody tures elucidated (13). Three monosaccharides ( -D-glucopyranose, β β β β with opsonophagocytic activity and representative of the protective -D-Glc; -D-galactopyranose, -D-Gal; and -D-N-acetylglucosamine, response against type III GBS polysaccharide.
    [Show full text]
  • Proinflammatory Action of a New Electronegative Low-Density Lipoprotein Epitope
    biomolecules Article Proinflammatory Action of a New Electronegative Low-Density Lipoprotein Epitope 1, 1, 1 Tanize do Espirito Santo Faulin y, Soraya Megumi Kazuma y, Gustavo Luis Tripodi , Marcela Frota Cavalcante 1, Felipe Wakasuqui 1, Cristiano Luis Pinto Oliveira 2, Maximilia Frazão de Souza Degenhardt 2, Jussara Michaloski 3, Ricardo José Giordano 3 , Daniel Francisco Jacon Ketelhuth 4,5 and Dulcineia Saes Parra Abdalla 1,* 1 Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil 2 Department of Experimental Physics, Institute of Physics, University of Sao Paulo, Sao Paulo 05508-090, Brazil 3 Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil 4 Centre for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Karolinska Institute, 17164 Stockholm, Sweden 5 Department of Cardiovascular and Renal Research, Institute for Molecular Medicine, University of Southern Denmark (SDU), 5000 Odense, Denmark * Correspondence: [email protected]; Tel.: +55-11-3091-3637 These authors contributed equally to this work. y Received: 13 July 2019; Accepted: 13 August 2019; Published: 20 August 2019 Abstract: The electronegative low-density lipoprotein, LDL ( ), is an endogenously modified − LDL subfraction with cytotoxic and proinflammatory actions on endothelial cells, monocytes, and macrophages contributing to the progression of atherosclerosis. In this study, epitopes of LDL ( ) were mapped using a phage display library of peptides and monoclonal antibodies reactive − to this modified lipoprotein. Two different peptide libraries (X6 and CX8C for 6- and 8-amino acid-long peptides, respectively) were used in the mapping. Among all tested peptides, two circular peptides, P1A3 and P2C7, were selected based on their high affinities for the monoclonal antibodies.
    [Show full text]
  • A Single Conformational Transglutaminase 2 Epitope Contributed by Three Domains Is Critical for Celiac Antibody Binding and Effects
    A single conformational transglutaminase 2 epitope contributed by three domains is critical for celiac antibody binding and effects Zsófia Simon-Vecseia, Róbert Királya,b, Péter Bagossia, Boglárka Tótha, Ingrid Dahlbomc, Sergio Cajad, Éva Csősza, Katri Lindforsd, Daniele Sblatteroe, Éva Nemesf, Markku Mäkid, László Fésüsa,b, and Ilma R. Korponay-Szabóf,g,1 aDepartment of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt 98, Debrecen H-4032, Hungary; bApoptosis and Genomics Research Group of Hungarian Academy of Sciences, Debrecen H-4032, Hungary; cDepartment of Women’s and Children’s Health, University of Uppsala, Uppsala SE-75185, Sweden; dPaediatric Research Centre, University of Tampere and Tampere University Hospital, Tampere, FIN-33014, Finland; eDepartment of Medical Sciences and Interdisciplinary Research Center of Autoimmune Disease (IRCAD), University of Eastern Piedmont, Novara 28100, Italy; fDepartment of Pediatrics, Medical and Health Science Center, University of Debrecen, Debrecen H-4032, Hungary; and gCeliac Disease Center, Heim Pál Children’s Hospital, Budapest H-1089, Hungary Edited by Michael Sela, Weizmann Institute of Science, Rehovot, Israel, and approved October 31, 2011 (received for review June 18, 2011) The multifunctional, protein cross-linking transglutaminase 2 (TG2) testinal inflammation, and villous atrophy in genetic susceptible is the main autoantigen in celiac disease, an autoimmune disorder individuals carrying HLA-DQ2 or DQ8 (4). with defined etiology. Glutamine-rich gliadin peptides from in- Celiac antibodies exert biological effects via TG2, partly by gested cereals, after their deamidation by TG2, induce T-lympho- gain in catalytic activity, on epithelial cell differentiation (5) and cyte activation accompanied by autoantibody production against transport (6), angiogenesis (7), vascular permeability (8), mono- TG2 in 1–2% of the population.
    [Show full text]