DOCSLIB.ORG

High-Throughput Sequencing of Natively Paired Antibody Chains

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
High-Throughput Sequencing of Natively Paired Antibody Chains Clinical Immunology (2014) 151,55–65 available at www.sciencedirect.com Clinical Immunology www.elsevier.com/locate/yclim High-throughput sequencing of natively paired antibody chains provides evidence for original antigenic sin shaping the antibody response to influenza vaccination Yann-Chong Tan a,b,c, Lisa K. Blum a,b, Sarah Kongpachith a,b,c, Chia-Hsin Ju a,b, Xiaoyong Cai a,b, Tamsin M. Lindstrom a, Jeremy Sokolove a,b, William H. Robinson a,b,c,⁎ a Division of Immunology and Rheumatology, Stanford University, CCSR 4135, 269 Campus Dr, Stanford, CA 94305, USA b VA Palo Alto Health Care System, 3801 Miranda Ave, Palo Alto, CA 94304, USA c Stanford Immunology Program, Stanford University School of Medicine, Stanford, CA 94305, USA Received 17 November 2013; accepted with revision 30 December 2013 KEYWORDS Abstract We developed a DNA barcoding method to enable high-throughput sequencing of the Antibody; cognate heavy- and light-chain pairs of the antibodies expressed by individual B cells. We used Influenza; this approach to elucidate the plasmablast antibody response to influenza vaccination. We show B cell that N75% of the rationally selected plasmablast antibodies bind and neutralize influenza, and that antibodies from clonal families, defined by sharing both heavy-chain VJ and light-chain VJ sequence usage, do so most effectively. Vaccine-induced heavy-chain VJ regions contained on average N20 nucleotide mutations as compared to their predicted germline gene sequences, and some vaccine-induced antibodies exhibited higher binding affinities for hemagglutinins derived from prior years' seasonal influenza as compared to their affinities for the immunization strains. Our results show that influenza vaccination induces the recall of memory B cells that express antibodies that previously underwent affinity maturation against prior years' seasonal influenza, suggesting that ‘original antigenic sin’ shapes the antibody response to influenza vaccination. Published by Elsevier Inc. ⁎ Corresponding author at: Division of Immunology and Rheumatology, Stanford University, CCSR 4135, 269 Campus Dr, Stanford, CA, 94305, USA. E-mail address: [email protected] (W.H. Robinson). 1521-6616/$ - see front matter Published by Elsevier Inc. http://dx.doi.org/10.1016/j.clim.2013.12.008 56 Y.-C. Tan et al. 1. Introduction responses, we developed a novel DNA barcoding method that combines high-throughput sequencing and barcode-enabled pairing of cognate heavy- and light-chain antibody sequences Despite the availability of seasonal influenza vaccination, expressed by individual B cells. This method enables the influenza continues be a major cause of morbidity and comprehensive analysis of antibody repertoires, followed by mortality in the US and worldwide [1,2]. Even the healthy the direct and efficient production of endogenous monoclonal adult population is vulnerable, as highlighted by the antibodies. significant morbidity and mortality during the 1918 and We describe use of this novel DNA barcoding method to 2009 pandemics [3,4]. Although influenza vaccination can characterize the plasmablast antibody response to influenza reduce influenza-associated morbidity and mortality, a vaccination. We focused our analysis on the antibodies meta-analysis of available data indicate that the trivalent expressed by plasmablasts circulating in the bloodstream inactivated influenza vaccine (TIV) is effective only in following influenza vaccination. We bioinformatically gen- approximately 60% of young adults [5], and the protection erated phylogenetic trees of the antibody response and afforded is significantly lower in those over age 65 [6].Asa rationally selected key antibodies for cloning, expression, result, there is great need to better understand the and characterization of their binding and functional proper- mechanisms underlying effective vs. non-effective vaccina- ties. Greater than 75% of the rationally selected plasmablast tion for influenza. antibodies bound and neutralized influenza, and antibodies TIV induces neutralizing antibodies that mediate protec- from clonal families (sharing heavy-chain V(D)J and tion against infection [2,7], and there are likely a variety of light-chain VJ sequences) do so most effectively. Some mechanisms underlying effective vs. non-effective vaccina- vaccine-induced antibodies exhibited higher binding affini- tion. Because immune responses wane with advancing ties for hemagglutinins derived from prior years' seasonal age, vaccination may not offer sufficient protection in the influenza as compared to their affinities for the immuniza- elderly, who account for N90% of influenza-related deaths tion strains. [1]. The inadequacy of protection in the elderly is in part due to their mounting an inferior antibody response [8]. 2. Materials and methods Compared to those in young adults, antibody repertoires in elderly individuals have a lower number of lineages and a higher pre-vaccination mutation load [9]. Deep sequencing 2.1. Single-cell sorting of plasmablasts of the immunoglobulin heavy-chain RNA present in peripheral blood mononuclear cells following repeat yearly influenza We collected blood from three individuals (Suppl. Table 1) vaccinations demonstrated direct genetic evidence of mem- vaccinated 7 days earlier with the 2010/2011 seasonal oryB-cellrecallresponses[10]. trivalent influenza vaccine (Sanofi Pasteur), which consists The immune history of individuals, specifically prior of 3 strains of inactivated influenza: H1N1 A/California/7/ infections with related pandemic H1N1 influenza strains, 2009, H3N2 A/Perth/16/2009, and B/Brisbane/60/2008. can shape the specificity of the pandemic H1N1 influenza Samples were collected after obtaining informed patient antibody responses to viral regions with shared homology consent and under human subject protocols approved by the [11]. Further, the antibody response to influenza vaccina- Investigational Review Board (IRB) at Stanford University. tion can include antibodies that react to a greater extent PBMCs were stained with CD3-V450 (BD 560365), IgA-FITC with influenza strains present in prior years' seasonal (AbD Serotec STAR142F or Miltenyi #130-093-071), IgM-FITC influenza to which an individual has been exposed (and not (AbD Serotec STAR146F), IgM-APC (BD 551062) or IgM-PE present in the current influenza strain), a phenomenon (AbD Serotec STAR146PE), CD20-PerCP-Cy5.5 (BD 340955), known as 'original antigenic sin' (OAS) [12–15]. CD38-PE-Cy7 (BD 335808), CD19-APC (BD 340437) or CD19- Secreted antibodies are produced by plasma cells and Brilliant Violet 421 (Biolegend 302233), and CD27-APC-H7 their B-cell precursors, termed plasmablasts [16–18]. After (BD 560222). We sorted cells with a BD FACSAria II or III, N becoming activated and undergoing antigen-dependent achieving purities of 80% from the first bulk sort. We gated + - + ++ − − affinity maturation, naïve and memory B cells differentiate on CD19 CD20 CD27 CD38 IgA IgM cells for the bulk into plasmablasts which proliferate, undergo affinity mat- plasmablast sort, and then single-cell sorted them into uration, and then traffic via the blood to infected tissues 96-well PCR plates containing a hypotonic buffer (10 mM – μ and secondary lymphoid organs [19]. Although plasmablast Tris HCl pH 7.6) comprised of 2 mM dNTPs (NEB), 5 M μ frequencies in peripheral blood are low before and after an oligo(dT)20VN, and 1 unit/ L of Ribolock (Fermentas), an immune response (~0.1% of circulating B cells), they can RNase inhibitor. account for 1–5% of peripheral blood B cells in response to influenza vaccination [17,20] and over 30% of circulating B 2.2. Reverse transcription with well-ID-containing cells during an immune response to an infection [16,21]. adapter Further, it has been demonstrated that the majority of plasmablasts generated in response to influenza vaccination We added 1 μM final concentration of the appropriate express influenza-reactive antibodies [14,17,20].Inthisstudy reverse transcription (RT) adapter molecule (each contain- we characterized the antibody repertoires of peripheral blood ing a unique well-ID barcode; listed in Suppl. Table 2) to plasmablasts to provide a ‘snapshot’ of the ongoing antibody each well, including the negative-control wells (containing response. no cells). We performed RT at 42 °C for 120 min in buffer To investigate antibody responses to vaccinations, to containing 6 mM MgCl2 with Ribolock and Superscript III (Life microbial infections, in autoimmunity, and in other immune Technologies). Following RT, the cDNA products from all Sequencing antibody repertoires provides evidence for original antigenic sin 57 wells of each plate were pooled together, extracted with 3.2. VJ and clonal family assignment phenol–chloroform–isoamyl alcohol followed by chloro- form, and concentrated and desalted in 5-minute spins at We analyzed heavy- and light-chain sequences with HighV- 14,000 g with Amicon Ultra-0.5 30 kDa (Millipore) units. QUEST [22], software that compares an antibody-chain sequence to a database of known alleles of germline sequences and predicts which germline alleles the antibody uses, how 2.3. Polymerase chain reaction (PCR) the germline sequences were recombined, and the number of mutations the antibody has relative to the germline We used Phusion Hot Start II DNA polymerase (NEB/ sequence (including all mutations, silent mutations, and Fermentas) for both the first PCR (PCR1) and the nested non-silent mutations). Clonal family antibodies were de- PCR (PCR2). Primers and adapter
Load more

Recommended publications
  • Original Antigenic Sin: a Comprehensive Review
    Journal of Autoimmunity 83 (2017) 12e21 Contents lists available at ScienceDirect Journal of Autoimmunity journal homepage: www.elsevier.com/locate/jautimm Review article Original antigenic sin: A comprehensive review Anup Vatti a, Diana M. Monsalve b, Yovana Pacheco b, Christopher Chang a, * Juan-Manuel Anaya b, M. Eric Gershwin a, a University of California at Davis, Division of Rheumatology, Allergy and Clinical Immunology, Suite 6501, 451 Health Sciences Drive, Davis, CA, 95616, USA b Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Carrera 24 No. 63-C-69, Bogota, Colombia article info abstract Article history: The concept of “original antigenic sin” was first proposed by Thomas Francis, Jr. in 1960. This phe- Received 27 March 2017 nomenon has the potential to rewrite what we understand about how the immune system responds to Received in revised form infections and its mechanistic implications on how vaccines should be designed. Antigenic sin has been 24 April 2017 demonstrated to occur in several infectious diseases in both animals and humans, including human Accepted 25 April 2017 influenza infection and dengue fever. The basis of “original antigenic sin” requires immunological Available online 5 May 2017 memory, and our immune system ability to autocorrect. In the context of viral infections, it is expected that if we are exposed to a native strain of a pathogen, we should be able to mount a secondary immune Keywords: “ ” Vaccination response on subsequent exposure to the same pathogen. Original antigenic sin will not contradict this Bocavirus well-established immunological process, as long as the subsequent infectious antigen is identical to the Dengue original one.
    [Show full text]
  • B Cell Responses Against Influenza Viruses
    viruses Review B Cell Responses against Influenza Viruses: Short-Lived Humoral Immunity against a Life-Long Threat Jenna J. Guthmiller 1,* , Henry A. Utset 1 and Patrick C. Wilson 1,2 1 Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA; [email protected] (H.A.U.); [email protected] (P.C.W.) 2 Committee on Immunology, University of Chicago, Chicago, IL 60637, USA * Correspondence: [email protected] Abstract: Antibodies are critical for providing protection against influenza virus infections. However, protective humoral immunity against influenza viruses is limited by the antigenic drift and shift of the major surface glycoproteins, hemagglutinin and neuraminidase. Importantly, people are exposed to influenza viruses throughout their life and tend to reuse memory B cells from prior exposure to generate antibodies against new variants. Despite this, people tend to recall memory B cells against constantly evolving variable epitopes or non-protective antigens, as opposed to recalling them against broadly neutralizing epitopes of hemagglutinin. In this review, we discuss the factors that impact the generation and recall of memory B cells against distinct viral antigens, as well as the immunological limitations preventing broadly neutralizing antibody responses. Lastly, we discuss how next-generation vaccine platforms can potentially overcome these obstacles to generate robust and long-lived protection against influenza A viruses. Keywords: influenza viruses; humoral immunity; broadly neutralizing antibodies; imprinting; Citation: Guthmiller, J.J.; Utset, H.A.; hemagglutinin; germinal center; plasma cells Wilson, P.C. B Cell Responses against Influenza Viruses: Short-Lived Humoral Immunity against a Life-Long Threat. Viruses 2021, 13, 1.
    [Show full text]
  • HLA, Immune Response, and Susceptibility to COVID-19
    REVIEW published: 08 January 2021 doi: 10.3389/fimmu.2020.601886 HLA, Immune Response, and Susceptibility to COVID-19 Fataneh Tavasolian 1, Mohsen Rashidi 2, Gholam Reza Hatam 3, Marjan Jeddi 4, Ahmad Zavaran Hosseini 5, Sayed Hussain Mosawi 6,7, Elham Abdollahi 8 and Robert D. Inman 1,9* 1 Spondylitis Program, Division of Rheumatology, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada, 2 Department of Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran, 3 Basic Sciences in Infectious Diseases Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran, 4 Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran, 5 Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran, 6 Medical Sciences Research Center, Ghalib University, Kabul, Afghanistan, 7 COVID-19 Directorate, Ministry of Public Health, Kabul, Afghanistan, 8 Department of Medical Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran, 9 Department of Medicine and Immunology, University of Toronto, Toronto, ON, Canada The severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2) that appeared in December 2019 has precipitated the global pandemic Coronavirus Disease 2019 (COVID-19). However, in many parts of Africa fewer than expected cases of COVID- Edited by: 19, with lower rates of mortality, have been reported. Individual human leukocyte antigen Ruchi Tiwari, U.P. Pandit Deen Dayal Upadhyaya (HLA) alleles can affect both the susceptibility and the severity of viral infections. In the case Veterinary University, India of COVID-19 such an analysis may contribute to identifying individuals at higher risk of the Reviewed by: disease and the epidemiological level to understanding the differences between countries Talha Bin Emran, fi fl Begum Gulchemonara Trust in the epidemic patterns.
    [Show full text]
  • High Seroreactivity Against SARS-Cov-2 Spike Epitopes in a Pre SARS-Cov-2 Cohort: Implications for Antibody Testing and Vaccine Design
    medRxiv preprint doi: https://doi.org/10.1101/2020.05.18.20105189; this version posted May 22, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . High seroreactivity against SARS-CoV-2 Spike epitopes in a pre SARS-CoV-2 cohort: implications for antibody testing and vaccine design Kaia Palm1*#, Mariliis Jaago1,2*, Annika Rähni1,2, Nadežda Pupina1, Arno Pihlak1, Helle Sadam1,2, Annela Avarlaid2, Anu Planken3, Margus Planken3, Liina Haring4, Eero Vasar5,6, Miljana Baćević7, France Lambert8, Eija Kalso9, Pirkko Pussinen10, Pentti J. Tienari11, Antti Vaheri12, Dan Lindholm13,14, Tõnis Timmusk1,2 and Amir M Ghaemmaghami15# 1Protobios Llc, Tallinn, Estonia. Electronic address: [email protected] 2Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, Estonia; 3North Estonia Medical Centre Foundation, Tallinn, Estonia; 4Institute of Clinical Medicine, University of Tartu, Psychiatry Clinic of Tartu University Hospital, Estonia; 5Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia; 6Center of Excellence for Genomics and Translational Medicine, University of Tartu, Tartu, Estonia; 7Dental Biomaterial Research Unit (d-BRU), Faculty of Medicine, University of Liege, Liege, Belgium; 8Department of Periodontology and Oral Surgery, Faculty of Medicine, University
    [Show full text]
  • Setting up Medium- and Long-Term Vaccine Strain Selection and Immunity Management for SARS-Cov-2
    Setting up medium- and long-term vaccine strain selection and immunity management for SARS-CoV-2 Executive Summary 1. SARS-CoV-2 is evolving antigenically. Some variants are less well neutralized by antibodies raised to current vaccines, and the vaccine efficacy against these variants is lower than for matched virus. 2. Administration of further doses of the current vaccine, which is based on the spike protein from the Wuhan-like virus that emerged in 2019, might maintain and/or boost protection into winter 2021/22, but potentially less so for individuals with a less robust immune response, and less so if substantially antigenically variant viruses circulate widely. Eventually it is likely that the virus will display sufficient substantial antigenic variation and current vaccines will fail to protect against transmission, infection, or even against disease caused by newer variants. 3. Loss of vaccine effectiveness will result in further economic and social costs. 4. A solution is to update vaccines to keep pace with virus evolution, and the newer, more flexible vaccine platforms are particularly suitable for this approach. 5. Additional potential solutions are to invest in developing new vaccination strategies that could induce stronger T cell responses since T cell epitopes might vary less over time. 6. Another strategy would be to search for more broadly protective vaccines, including universal vaccine candidates, multivalent vaccines, and heterologous prime-boost strategies 7. We should also consider whether future vaccination policy will aim to immunize the whole population or only those at risk from severe disease, and how this might be impacted by the long-term accumulation of baseline immunity in the population and long-term evolution of the virus.
    [Show full text]
  • The Future for Influenza Preimmunity—Looking Back at Influenza Virus
    viruses Review Back to the Future for Influenza Preimmunity—Looking Back at Influenza Virus History to Infer the Outcome of Future Infections Magen Ellen Francis 1, Morgan Leslie King 1 and Alyson Ann Kelvin 1,2,3,* 1 Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, NS B3K 6R8, Canada; [email protected] (M.E.F.); [email protected] (M.L.K.) 2 Department of Pediatrics, Division of Infectious Disease, Faculty of Medicine, Dalhousie University, Halifax, NS B3K 6R8, Canada 3 Canadian Centre for Vaccinology, IWK Health Centre, Halifax NS B3K 6R8, Canada * Correspondence: [email protected]; Tel.: +1-902-470-2760 Received: 21 December 2018; Accepted: 22 January 2019; Published: 30 January 2019 Abstract: The influenza virus-host interaction is a classic arms race. The recurrent and evolving nature of the influenza virus family allows a single host to be infected several times. Locked in co-evolution, recurrent influenza virus infection elicits continual refinement of the host immune system. Here we give historical context of circulating influenza viruses to understand how the individual immune history is mirrored by the history of influenza virus circulation. Original Antigenic Sin was first proposed as the negative influence of the host’s first influenza virus infection on the next and Imprinting modernizes Antigenic Sin incorporating both positive and negative outcomes. Building on imprinting, we refer to preimmunity as the continual refinement of the host immune system with each influenza virus infection. We discuss imprinting and the interplay of influenza virus homology, vaccination, and host age establishing preimmunity. We outline host signatures and outcomes of tandem infection according to the sequence of virus and classify these relationships as monosubtypic homologous, monosubtypic heterologous, heterosubtypic, or heterotypic sequential infections.
    [Show full text]
  • Original Antigenic Sin Priming of Influenza Virus Hemagglutinin Stalk Antibodies
    Original antigenic sin priming of influenza virus hemagglutinin stalk antibodies Claudia P. Arevaloa, Valerie Le Sageb, Marcus J. Boltona, Theresa Eilolaa, Jennifer E. Jonesb, Karen A. Kormuthb, Eric Nturibib, Angel Balmasedac, Aubree Gordond, Seema S. Lakdawalab,e, and Scott E. Hensleya,1 aDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; bDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219; cCentro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua 16064; dDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109; and eCenter for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219 Edited by Michael B.A. Oldstone, Scripps Research Institute, La Jolla, CA, and approved May 27, 2020 (received for review November 18, 2019) Immunity to influenza viruses can be long-lived, but reinfections but there are more conserved epitopes in the HA stalk domain. with antigenically distinct viral strains and subtypes are common. Antibodies that recognize the HA stalk of group 1 or group 2 Reinfections can boost antibody responses against viral strains viruses have been well characterized, but antibodies that recog- first encountered in childhood through a process termed “original nize the HA stalk of both group 1 and group 2 viruses are rare antigenic sin.” It is unknown how initial childhood exposures af- (15, 16). Interestingly, childhood influenza A virus exposures are fect the induction of antibodies against the hemagglutinin (HA) associated with heterosubtypic protection against distinct stalk domain of influenza viruses. This is an important consider- emerging influenza virus subtypes later in life (13).
    [Show full text]
  • Strategies to Alleviate Original Antigenic Sin Responses to Influenza
    Strategies to alleviate original antigenic sin responses to influenza viruses Jin Hyang Kima,1, William G. Davisb, Suryaprakash Sambharab, and Joshy Jacoba,2 aDepartment of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Center, Emory University, Atlanta, GA 30329; and bImmunology and Pathogenesis Branch, Influenza Division, National Centers for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329 Edited* by Leonard A. Herzenberg, Stanford University, Stanford, CA, and approved July 10, 2012 (received for review November 4, 2009) Original antigenic sin is a phenomenon wherein sequential expo- (11), and its components including B. pertussis toxin (PT) and B. sure to closely related influenza virus variants reduces antibody pertussis endotoxin (LPS) have been shown to block or reverse (Ab) response to novel antigenic determinants in the second strain carrier-mediated hapten suppression (12, 13). Specifically, PT and, consequently, impairs the development of immune memory. stimulates DCs to up-regulate MHC class II and costimulatory This could pose a risk to the development of immune memory in molecules [cluster of differentiation (CD)80, CD86, CD40, and fl dendritic and epithelial cell (DEC)205] to produce IL-12 and persons previously infected with or vaccinated against in uenza. α Here, we explored strategies to overcome original antigenic sin TNF- and to up-regulate phosphorylation of ERK (14). This overall DC activation by PT elicits a Th1 response by promoting responses in mice sequentially exposed to two closely related γ fl T cells to produce IFN- . Bacterial DNA containing unmethy- hemagglutinin 1 neuraminidase 1 (H1N1) in uenza strains A/PR/8/ lated CpG-dinucleotide is also a strong adjuvant for Th1 re- 34 and A/FM/1/47.
    [Show full text]
  • Immune Response to DENV
    Learn More Dengue Clinical Case Management E-learning Immune Response to DENV DENV infected antigen presenting cells (APC) within the lymph node recruit T cells through the production of chemoattractants. The APCs process the foreign DENV proteins into small pieces for display on the cell surface. T cells that recognize the presented antigen become activated and produce pro-inflammatory mediators. This results in the activation of the two major branches of the adaptive immune response: • Humoral immunity: helper cells make pro-inflammatory mediators that activate B cells to make antibody to eliminate DENV • Cell-mediated immunity: cytotoxic T cells directly kill cells infected with DENV Development of Life-long Type Specific Immunity Soon after DENV infection, B cells become activated, proliferate and produce IgM against the infecting DENV type. Later, some B cells change to produce IgG (some IgA or IgE, too); however, the specificity of the antibody is the same. A subset of B cells become memory cells that provide life- long protection against the infecting DENV type. Serotype Cross-Reactivity in Dengue DENV types have similar envelope or E proteins so during infection, cross-reactive (heterotypic) antibodies against all DENV types are made. DENV types are immunologically distinct and induce the production of antibodies that are type-specific (homotypic). Centers for Disease Control and Prevention 1 National Center for Emerging and Zoonotic Infectious Diseases Learn More Dengue Clinical Case Management E-learning Immune Response to DENV Secondary DENV Infections If a person is re-infected with the same DENV type, memory B cells recognize it and will start to divide, resulting in the production of new B cells that make homotypic IgG and memory cells.
    [Show full text]
  • Immunology and Evolution of Infectious Disease
    Immunology and Evolution of Infectious Disease STEVEN A. FRANK Princeton University Press Princeton and Oxford Copyright © 2002 by Steven A. Frank Published by Princeton University Press, 41 William Street, Princeton, New Jersey 08540 In the United Kingdom: Princeton University Press, 3MarketPlace,Woodstock, Oxfordshire OX20 1SY All Rights Reserved Library of Congress Cataloging-in-Publication Data Frank, Steven A., 1957– Immunology and Evolution of Infectious Disease / Steven A. Frank. p. cm. Includes bibliographic references and index. ISBN 0–691–09594–9 (cloth : alk. paper) ISBN 0–691–09595–7 (pbk. : alk. paper) 1. Immunogenetics. 2. Host-parasite relationships— Genetic aspects. 3. Microorganisms—Evolution. 4. Antigens. 5. Molecular evolution. 6. Parasite antigens—Variation. I. Title. [DNLM: 1. Communicable Diseases—immunology. 2. Evolution, Molecular. 3. Genetics, Population. 4. Immunity—genetics. WC 100 F828i 2002] QR184 .F73 2002 616.9 0479—dc21 2002018384 British Library Cataloging-in-Publication Data is available Typeset by the author with TEX Composed in Lucida Bright Printed on acid-free paper. ∞ www.pupress.princeton.edu Printed in the United States of America 10 9 87654321 10 9 87654321 (Pbk.) Contents Acknowledgments xi 1 Introduction 3 PART I: BACKGROUND 2 Vertebrate Immunity 13 2.1 Nonspecific Immunity 14 2.2 Specific Immunity: Antigens andEpitopes 15 2.3 BCells and Antibodies 16 2.4 TCells and MHC 19 2.5 Summary 20 3 Benefits of Antigenic Variation 22 3.1 Extend Length of Infection 23 3.2 Infect Hosts withPriorExposure 24
    [Show full text]
  • Optimal Evolutionary Decision-Making to Store Immune Memory Oskar H Schnaack1,2, Armita Nourmohammad1,2,3*
    RESEARCH ARTICLE Optimal evolutionary decision-making to store immune memory Oskar H Schnaack1,2, Armita Nourmohammad1,2,3* 1Max Planck Institute for Dynamics and Self-organization, Go¨ ttingen, Germany; 2Department of Physics, University of Washington, Seattle, United States; 3Fred Hutchinson Cancer Research Center, Seattle, United States Abstract The adaptive immune system provides a diverse set of molecules that can mount specific responses against a multitude of pathogens. Memory is a key feature of adaptive immunity, which allows organisms to respond more readily upon re-infections. However, differentiation of memory cells is still one of the least understood cell fate decisions. Here, we introduce a mathematical framework to characterize optimal strategies to store memory to maximize the utility of immune response over an organism’s lifetime. We show that memory production should be actively regulated to balance between affinity and cross-reactivity of immune receptors for an effective protection against evolving pathogens. Moreover, we predict that specificity of memory should depend on the organism’s lifespan, and shorter lived organisms with fewer pathogenic encounters should store more cross-reactive memory. Our framework provides a baseline to gauge the efficacy of immune memory in light of an organism’s coevolutionary history with pathogens. Introduction Adaptive immunity in vertebrates develops during the lifetime of an organism to battle a multitude of evolving pathogens. The central actors in our adaptive immune system are diverse B- and T-cells, *For correspondence: whose unique surface receptors are generated through genomic rearrangement, mutation, and [email protected] selection (Janeway et al., 2005). The diversity of receptors allows the immune system to mount spe- cific responses against diverse pathogens.
    [Show full text]
  • Evidence for Deleterious Original Antigenic Sin in SARS-Cov-2
    bioRxiv preprint doi: https://doi.org/10.1101/2021.05.21.445201; this version posted May 24, 2021. 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 Evidence for Deleterious Original Antigenic Sin in 2 SARS-CoV-2 Immune Response 3 Sanjana R. Sen1, Emily C. Sanders2, Alicia M. Santos2, Keertna Bhuvan2, Derek Y. Tang2, 4 Aidan A. Gelston2, Brian M. Miller2, Joni L. Ricks-Oddie3,4 and Gregory A. Weiss1,2,5* 5 6 Author Affiliations: 7 1 Department of Molecular Biology & Biochemistry, University of California, Irvine, Irvine CA 92697-3900 USA 8 2 Department of Chemistry, University of California, Irvine, Irvine CA 92697-2025 USA 9 3 Center for Statistical Consulting, Department of Statistics, University of California, Irvine, Irvine CA 92697-1250 10 USA 11 4 Biostatics, Epidemiology and Research Design Unit, Institute for Clinical and Translational Sciences, University of 12 California, Irvine, Irvine CA 92697-4094 USA 13 5 Department of Pharmaceutical Sciences, University of California, Irvine, Irvine CA 92697-3958 USA 14 15 * Address correspondence to [email protected] 16 17 Corresponding Author: 18 *GAW e-mail: [email protected], Tel: +1-949-824-5566, address: 1102 Natural Sciences 2, Irvine, CA 92697-2025, 19 USA 20 21 Author Contributions: 22 S.R.S., and G.A.W. designed research; S.R.S., E.C.S., A.M.S., K.B., D.Y.T, A.A.G., and B.M.M. performed research; 23 S.R.S., E.C.S.
    [Show full text]