DOCSLIB.ORG

Cells by Virus-Induced Molecular Mimicry Functional Activation Of

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cells by Virus-Induced Molecular Mimicry Functional Activation Of Functional Activation of Myelin-Specific T Cells by Virus-Induced Molecular Mimicry Julie K. Olson, Todd N. Eagar and Stephen D. Miller This information is current as J Immunol 2002; 169:2719-2726; ; of September 26, 2021. doi: 10.4049/jimmunol.169.5.2719 http://www.jimmunol.org/content/169/5/2719 Downloaded from References This article cites 34 articles, 13 of which you can access for free at: http://www.jimmunol.org/content/169/5/2719.full#ref-list-1 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 26, 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 © 2002 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Functional Activation of Myelin-Specific T Cells by Virus-Induced Molecular Mimicry1 Julie K. Olson, Todd N. Eagar, and Stephen D. Miller2 Molecular mimicry is the process by which T cells activated in response to determinants on an infecting microorganism cross-react with self epitopes, leading to an autoimmune disease. Normally, infection of SJL/J mice with the BeAn strain of Theiler’s murine encephalomyelitis virus (TMEV) results in a persistent CNS infection, leading to a chronic progressive, CD4؉ T cell-mediated demyelinating disease. Myelin damage is initiated by T cell responses to virus persisting in CNS APCs, and progressive demy- elinating disease (50 days postinfection) is perpetuated by myelin epitope-specific CD4؉ T cells activated by epitope spreading. We developed an infectious model of molecular mimicry by inserting a sequence encompassing the immunodominant myelin epitope, proteolipid protein (PLP) 139–151, into the coding region of a nonpathogenic TMEV variant. PLP139-TMEV-infected mice ؉ developed a rapid onset paralytic inflammatory, demyelinating disease paralleled by the activation of PLP139–151-specific CD4 Downloaded from Th1 responses within 10–14 days postinfection. The current studies demonstrate that the early onset demyelinating disease induced by PLP139-TMEV is the direct result of autoreactive PLP139–151-specific CD4؉ T cell responses. PLP139–151-specific CD4؉ T cells from PLP139-TMEV-infected mice transferred demyelinating disease to naive recipients and PLP139–151-specific tolerance before infection prevented clinical disease. Finally, infection with the mimic virus at sites peripheral to the CNS induced early demyelinating disease, suggesting that the PLP139–151-specific CD4؉ T cells could be activated in the periphery and traffic to the CNS. Collectively, infection with PLP139–151 mimic encoding TMEV serves as an excellent model for molecular mimicry http://www.jimmunol.org/ :by inducing pathologic myelin-specific CD4؉ T cells via a natural virus infection. The Journal of Immunology, 2002, 169 2719–2726. utoimmune diseases have been suggested to be initiated ular mimicry in autoimmune disease, the evidence was indirect in and perpetuated as a result of virus infections. Three that autoreactivity was not induced as a direct consequence of A possible mechanisms have been suggested for initiating infection. Recently, several reports have provided more direct ev- autoimmune disease following virus infection: bystander activa- idence of infection-induced molecular mimicry by showing that tion, molecular mimicry, and epitope spreading (reviewed in Ref. infection with HSV type I leads to the development of herpes 1). Molecular mimicry is the process by which cross-reactive T stromal keratitis, an inflammatory eye disease (10), and that a by guest on September 26, 2021 cells are generated during a virus infection that recognizes both Theiler’s virus variant engineered to encode a molecular mimic of viral and self epitopes (2). Over the past decade, evidence for a an encephalitogenic proteolipid protein epitope (PLP139–151)3 role of molecular mimicry in the initiation of autoimmune diseases could induce demyelinating disease upon infection (11). has resulted from a number of approaches. Initial molecular mim- Multiple sclerosis (MS) is a CD4ϩ T cell-mediated autoimmune icry studies showed that transgenic mice expressing virus proteins demyelinating disease affecting humans that has a suspected virus in the context of self tissues developed autoimmune disease fol- etiology (12). Theiler’s murine encephalomyelitis virus (TMEV)- lowing infection with the corresponding virus (3, 4). Previous induced demyelinating disease serves as a relevant mouse model studies have also demonstrated that viral peptides sharing limited of MS due to numerous pathological and immunological similar- sequence homology with self myelin peptides could stimulate au- ities (13). Infection of susceptible SJL/J mice with the BeAn strain toreactive T cell clones isolated from patients with multiple scle- of TMEV results in a chronic progressive CD4ϩ T cell-mediated rosis (5, 6). Mimic epitopes have been identified in Borrelia burg- CNS demyelinating disease onsetting 30–35 days postinfection dorferi that may be involved in Lyme arthritis and neuroborreliosis and characterized by persistent infection of CNS microglia (14). using patient T cell clones (7, 8), and heart disease was shown to Myelin destruction is initiated by virus-specific CD4ϩ T cells that be induced by immunizing mice with a Chlamydia pneumoniae eventually lead to the activation of myelin-specific, autoreactive peptide that shared sequence homology with heart-muscle protein CD4ϩ T cells via epitope spreading, with responses to PLP139– (9). Although these studies provided support for a role of molec- 151 first detected at 50 days postinfection (15, 16). Therefore, TMEV-induced demyelinating disease is a highly relevant model for studying virus-initiated autoimmune disease. Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, IL 60611 Recently, we developed a molecular mimicry model for initia- tion of autoimmune demyelination following virus infection with Received for publication March 22, 2002. Accepted for publication June 20, 2002. TMEV containing a self myelin epitope (11). Native or mimic The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance sequences of the immunodominant PLP139–151 epitope were in- with 18 U.S.C. Section 1734 solely to indicate this fact. serted into a nonpathogenic TMEV variant. Infection of SJL mice 1 This work was supported by U.S. Public Health Service National Institutes of Health Research Grants NS34819, NS30871, and AI/DK-51973, and National Multiple Scle- rosis Society Grant RG2275. 3 Abbreviations used in this paper: PLP, proteolipid protein; DTH, delayed-type hy- 2 Address correspondence and reprint requests to Dr. Stephen D. Miller, Department persensitivity; EAE, experimental autoimmune encephalomyelitis; i.c., intracerebral; of Microbiology-Immunology, Northwestern University Medical School, 303 East MBP, myelin basic protein; MS, multiple sclerosis; SI, stimulation index; SP, spleno- Chicago Avenue, Chicago, IL 60611. E-mail address: [email protected] cyte; TMEV, Theiler’s murine encephalomyelitis virus; WT, wild type. Copyright © 2002 by The American Association of Immunologists, Inc. 0022-1767/02/$02.00 2720 MYELIN-SPECIFIC AUTOIMMUNITY INDUCED BY VIRUS INFECTION with TMEV encoding native mouse PLP139–151, an altered pep- was determined with triplicate wells for each peptide concentration and tide ligand of PLP139–151, or a PLP139–151 mimic present in then expressed as cpm Ϯ SEM. The stimulation index (SI) was calculated the protease IV protein of Hemophilus influenzae induced a rapid by dividing cpm in experimental wells by the cpm in PBS-containing wells. For cytokine analysis, a duplicate set of proliferation wells was used to onset demyelinating disease associated with the induction of ϩ collect supernatants at 48 and 72 h. Supernatants were analyzed for IL-2, PLP139–151-specific CD4 T cell responses. The current studies IFN-␥, or IL-5 secretion by ELISA (Endogen, Cambridge, MA). were conducted to determine whether the early onset demyelinat- ing disease occurred directly through early activation of PLP139– Coupled cell tolerance 151-specific CD4ϩ T cells. The results show that the PLP139– 151-specific CD4ϩ T cells induced in PLP139-TMEV-infected Spleens were removed from naive mice and mechanically disrupted, and mice were encephalitogenic, as demonstrated by serial transfer of the RBCs were lysed. The splenocytes were incubated with ethylcarbodi- imide (150 mg/ 3.2 ϫ 108 cells) and peptide (1 mg/ml PLP139–151 or these T cells to naive mice, and that infection of mice with OVA 323–339) on ice, shaking periodically for 2 h. The coupled cells were PLP139-TMEV at sites peripheral to the CNS resulted in activa- washed and centrifuged to remove cell clumps. The single cell
Load more

Recommended publications
  • Molecular Mimicry Between Anoctamin 2 and Epstein-Barr Virus Nuclear Antigen 1 Associates with Multiple Sclerosis Risk
    Molecular mimicry between Anoctamin 2 and Epstein- Barr virus nuclear antigen 1 associates with multiple sclerosis risk Katarina Tengvalla,b,1, Jesse Huanga,b, Cecilia Hellströmc, Patrick Kammerd, Martin Biströme, Burcu Ayogluf, Izaura Lima Bomfima,b,PernillaStridha,b, Julia Buttd,NicoleBrennerd,AngelikaMicheld, Karin Lundbergb,g, Leonid Padyukovb,g, Ingrid E. Lundbergb,g, Elisabet Svenungssong, Ingemar Ernbergh, Sigurgeir Olafssoni, Alexander T. Diltheyj,k, Jan Hillerta, Lars Alfredssonl,m, Peter Sundströme, Peter Nilssonc,2, Tim Waterboerd,2, Tomas Olssona,b,2, and Ingrid Kockuma,b,2 aNeuroimmunology Unit, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Department of Clinical Neuroscience, Karolinska Institute, 171 76 Stockholm, Sweden; bCentrum for Molecular Medicine, Karolinska University Hospital, 171 76 Stockholm, Sweden; cDivision of Affinity Proteomics, Department of Protein Science, SciLifeLab, KTH - Royal Institute of Technology, 171 21, Solna, Sweden; dInfections and Cancer Epidemiology, Infection, Inflammation and Cancer Research Program, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; eDepartment of Pharmacology and Clinical Neuroscience, Umeå University, 901 85 Umeå, Sweden; fDivision of Cellular and Clinical Proteomics, Department of Protein Science, SciLifeLab, KTH - Royal Institute of Technology, 171 21, Solna, Sweden; gDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, 171 76 Stockholm, Sweden; hDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute,
    [Show full text]
  • 030710 Molecular Mimicry in Multiple Sclerosis
    The new england journal of medicine clinical implications of basic research Molecular Mimicry in Multiple Sclerosis Hartmut Wekerle, M.D., and Reinhard Hohlfeld, M.D. Most experts believe that multiple sclerosis is an senting cells expressed only the relevant HLA-DR2 autoimmune disease in which T cells recognize and restriction molecules. Normally, in HLA-DR2–pos- attack components of the axonal myelin sheath and itive persons, antigen-presenting cells (which in- other features of the central nervous system, de- clude dendritic cells, macrophages, and B cells) ex- stroying myelin and the underlying axon. Although self-reactive T cells are present in the immune sys- tem of people with multiple sclerosis, they are also found in a quiescent state in perfectly healthy peo- ple. Their pathogenic potential is realized only on acute activation, which can occur through different mechanisms. Recent work by Lang and colleagues focused on molecular mimicry, one of the presumed 1 T-cell receptor triggers of autoimmunity. Hy.2E11 Lang and coworkers investigated the antigen- specific T-cell receptor of a particular T-cell clone Epstein–Barr Myelin basic (Hy.2E11), originally isolated from the blood of a virus peptide protein peptide patient with multiple sclerosis. The clone was se- lected for its reactivity to a self antigen — the mye- lin basic protein (MBP) — but it was later found to cross-react with a peptide analogous to part of a viral antigen, the polymerase of the Epstein–Barr virus (EBV).2 The new work shows that this dual response is more complex than anticipated. The mimicry is not simply explained by the structural similarity of the two peptides, as posited by the original model of autoimmune mimicry,3 in which a foreign antigen HLA-DR2a HLA-DR2b is sufficiently similar to a self antigen to trigger an autoimmune response.
    [Show full text]
  • Review Article Infectious Diseases and Autoimmunity
    Review Article Infectious diseases and autoimmunity Lucia G. Delogu1, Silvia Deidda2, Giuseppe Delitala2, Roberto Manetti2 1Department of Drug Science, University of Sassari, Italy 2Department of Clinical, Experimental and Oncological Medicine, University of Sassari, Italy Abstract Introduction: Autoimmunity occurs when the immune system recognizes and attacks host tissue. In addition to genetic factors, environmental triggers (in particular viruses, bacteria and other infectious pathogens) are thought to play a major role in the development of autoimmune diseases. Methodology: We searched PubMed, Cochrane, and Scopus without time limits for relevant articles. Results: In this review, we (i) describe the ways in which an infectious agent can initiate or exacerbate autoimmunity; (ii) discuss the evidence linking certain infectious agents to autoimmune diseases in humans; and (iii) describe the animal models used to study the link between infection and autoimmunity. Conclusions: Besides genetic predisposition to autoimmunity, viral and bacterial infections are known to be involved in the initiation and promotion of autoimmune diseases. These studies suggest that pathogens can trigger autoimmunity through molecular mimicry and their adjuvant effects during initiation of disease, and can promote autoimmune responses through bystander activation or epitope spreading via inflammation and/or superantigens. Key words: viral infection; bacterial infection; autoreactive lymphocyte; molecular mimicry; bystander activation; epitope spreading; autoimmune disease J Infect Dev Ctries 2011; 5(10):679-687. (Received 03 May 2011 – Accepted 29 June 2011) Copyright © 2011 Delogu et al. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    [Show full text]
  • Antigen Mimicry-Recognizing Paratope
    Structural Evaluation of a Mimicry-Recognizing Paratope: Plasticity in Antigen−Antibody Interactions Manifests in Molecular Mimicry This information is current as of September 28, 2021. Suman Tapryal, Vineet Gaur, Kanwal J. Kaur and Dinakar M. Salunke J Immunol published online 3 June 2013 http://www.jimmunol.org/content/early/2013/06/01/jimmun ol.1203260 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 28, 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 © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published June 3, 2013, doi:10.4049/jimmunol.1203260 The Journal of Immunology Structural Evaluation of a Mimicry-Recognizing Paratope: Plasticity in Antigen–Antibody Interactions Manifests in Molecular Mimicry Suman Tapryal,*,1 Vineet Gaur,*,1 Kanwal J. Kaur,* and Dinakar M. Salunke*,† Molecular mimicry manifests antagonistically with respect to the specificity of immune recognition. However, it often occurs because different Ags share surface topologies in terms of shape or chemical nature.
    [Show full text]
  • The Role of Herpes Simplex Virus Type 1 Infection in Demyelination of the Central Nervous System
    International Journal of Molecular Sciences Review The Role of Herpes Simplex Virus Type 1 Infection in Demyelination of the Central Nervous System Raquel Bello-Morales 1,2,* , Sabina Andreu 1,2 and José Antonio López-Guerrero 1,2 1 Departamento de Biología Molecular, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain; [email protected] (S.A.); [email protected] (J.A.L.-G.) 2 Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Cantoblanco, 28049 Madrid, Spain * Correspondence: [email protected] Received: 30 June 2020; Accepted: 15 July 2020; Published: 16 July 2020 Abstract: Herpes simplex type 1 (HSV-1) is a neurotropic virus that infects the peripheral and central nervous systems. After primary infection in epithelial cells, HSV-1 spreads retrogradely to the peripheral nervous system (PNS), where it establishes a latent infection in the trigeminal ganglia (TG). The virus can reactivate from the latent state, traveling anterogradely along the axon and replicating in the local surrounding tissue. Occasionally, HSV-1 may spread trans-synaptically from the TG to the brainstem, from where it may disseminate to higher areas of the central nervous system (CNS). It is not completely understood how HSV-1 reaches the CNS, although the most accepted idea is retrograde transport through the trigeminal or olfactory tracts. Once in the CNS, HSV-1 may induce demyelination, either as a direct trigger or as a risk factor, modulating processes such as remyelination, regulation of endogenous retroviruses, or molecular mimicry. In this review, we describe the current knowledge about the involvement of HSV-1 in demyelination, describing the pathways used by this herpesvirus to spread throughout the CNS and discussing the data that suggest its implication in demyelinating processes.
    [Show full text]
  • Butyrophilin, a Milk Protein, Modulates the Encephalitogenic T Cell Response to Myelin Oligodendrocyte Glycoprotein in Experimental Autoimmune Encephalomyelitis1
    Butyrophilin, a Milk Protein, Modulates the Encephalitogenic T Cell Response to Myelin Oligodendrocyte Glycoprotein in Experimental Autoimmune Encephalomyelitis1 Andreas Stefferl,2*† Anna Schubart,2* Maria Storch,2†‡ Aminullah Amini,§ Ian Mather,§ Hans Lassmann,† and Christopher Linington3* Experimental autoimmune encephalomyelitis (EAE) induced by sensitization with myelin oligodendrocyte glycoprotein (MOG) is a T cell-dependent autoimmune disease that reproduces the inflammatory demyelinating pathology of multiple sclerosis. We report that an encephalitogenic T cell response to MOG can be either induced or alternatively suppressed as a consequence of immunological cross-reactivity, or “molecular mimicry” with the extracellular IgV-like domain of the milk protein butyrophilin (BTN). In the Dark Agouti rat, active immunization with native BTN triggers an inflammatory response in the CNS characterized by the formation of scattered meningeal and perivascular infiltrates of T cells and macrophages. We demonstrate that this pathology is mediated by a MHC class II-restricted T cell response that cross-reacts with the MOG peptide sequence 76–87, IGEGKVALRIQN (identities underlined). Conversely, molecular mimicry with BTN can be exploited to suppress disease activity in MOG-induced EAE. We demonstrate that not only is EAE mediated by the adoptive transfer of MOG74–90 T cell lines markedly ameliorated by i.v. treatment with the homologous BTN peptide, BTN74–90, but that this protective effect is also seen in actively induced disease following transmucosal
    [Show full text]
  • 4 Antibodies from Other Species Melissa L
    85 4 Antibodies from Other Species Melissa L. Vadnais1, Michael F. Criscitiello2, and Vaughn V. Smider1 1Department of Molecular Medicine, The Scripps Research Institute, 10550 N. Torrey Pines, La Jolla, CA 92037, USA 2Texas A&M University, College of Veterinary Medicine and Biomedical Sciences, Department of Veterinary Pathobiology, 400 Raymond Stotzer Parkway, College Station, TX 77843, USA 4.1 Introduction Immunoglobulins are the molecular basis of humoral immunity. Across different species, these macromolecules maintain a common quaternary structure, which is typically comprised of two identical heavy chains with covalently attached oligosaccharide groups and two identical non-glycosylated, light chains. These glycoprotein molecules recognize and bind a particular antigen in a highly complex and exceedingly specific immune response. Antibodies are the primary protective molecules elicited by most vaccines, and recombinant antibodies are now a major class of therapeutics for multiple diseases. The earliest antibody therapeutics were derived from serum of nonhuman species. In particular, horse serum served as anti-venom yet had substantial toxicity (serum sickness) due totheimmuneresponseagainstthenonhumanantibodyprotein[1,2].Other antibody preparations such as anti-thymocyte globulin produced in rabbit had therapeutic benefit but also had significant toxicity. The use of alternative species for these therapeutic preparations was largely due to ease of production, as they were developed prior to the advent of modern molecular biology techniques, which have enabled rapid discovery and engineering of recombinant antibodies. Thus, most current approaches for producing recombinant antibodies rely on humanizing antibodies derived from other species, usually mice, or beginning with human scaffolds engineered into libraries or transgenic “humanized” mice. Recently, however, novel features of antibodies derived from other species have sparked interest in developing antibodies that may have particular unique features in binding certain antigens or epitopes [3–7].
    [Show full text]
  • Autoimmunity
    RESEARCH HIGHLIGHTS Nature Reviews Immunology | AOP, published online 11 November 2011; doi:10.1038/nri3114 AUTOIMMUNITY Linking commensals with autoimmunity Autoimmune disorders develop myelin oligodendrocyte glycoprotein commensal bacteria in the gut and under the combined influence of (MOG). As disease incidence in the subsequent proliferation of these both environmental and genetic factors. these transgenic mice varies among T cells. commensal A recent study published in Nature different animal facilities, the authors In addition to the increased + bacteria and reports that both commensal bacteria asked whether the composition of the activation of autoreactive CD4 and self-antigen recognition are intestinal microbiota might have a T cells, B cells are crucial for disease self-antigen required for the initiation of auto­ role in EAE development. development. Serum from SPF trans- recognition are immune responses in relapsing– Indeed, whereas 80% of the trans- genic mice contained higher levels of required for remitting experimental autoimmune genic mice housed under specific MOG-specific IgG2a antibodies than the initiation encephalomyelitis (EAE), a mouse pathogen-free (SPF) conditions serum from germ-free transgenic model of multiple sclerosis. developed EAE, transgenic mice mice. However, the induction of of autoimmune The intestinal microbiota actively housed under germ-free conditions MOG-specific B cell responses in responses regulates local immune responses, showed no disease symptoms. This SPF transgenic mice did not rely on partly through the induction of effect was not due to differential molecular mimicry between MOG interleukin‑17 (IL‑17)-producing maturation of the immune system, epitopes and epitopes provided by T cells and regulatory T cells, but its as active immunization with recom- commensal bacteria, but was depend- contribution to immune responses binant MOG induced autoimmune ent on self-antigen expression, as at distal sites is largely unknown.
    [Show full text]
  • Vaccine-Induced Autoimmunity: the Role of Molecular Mimicry and Immune Crossreaction
    Cellular & Molecular Immunology (2018) 15, 586–594 & 2018 CSI and USTC All rights reserved 2042-0226/18 $32.00 www.nature.com/cmi REVIEW Vaccine-induced autoimmunity: the role of molecular mimicry and immune crossreaction Yahel Segal1 and Yehuda Shoenfeld1,2 Since the early 1800s vaccines have saved numerous lives by preventing lethal infections. However, during the past two decades, there has been growing awareness of possible adverse events associated with vaccinations, cultivating heated debates and leading to significant fluctuations in vaccination rates. It is therefore pertinent for the scientific community to seriously address public concern of adverse effects of vaccines to regain public trust in these important medical interventions. Such adverse reactions to vaccines may be viewed as a result of the interaction between susceptibility of the vaccinated subject and various vaccine components. Among the implicated mechanisms for these reactions is molecular mimicry. Molecular mimicry refers to a significant similarity between certain pathogenic elements contained in the vaccine and specific human proteins. This similarity may lead to immune crossreactivity, wherein the reaction of the immune system towards the pathogenic antigens may harm the similar human proteins, essentially causing autoimmune disease. In this review, we address the concept of molecular mimicry and its application in explaining post vaccination autoimmune phenomena. We further review the principal examples of the influenza, hepatitis B, and human papilloma virus vaccines,
    [Show full text]
  • Coronavirus Associated Molecular Mimicry Common to SARS-Cov-2 Peptide
    bioRxiv preprint doi: https://doi.org/10.1101/2021.01.28.428642; this version posted January 28, 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. Coronavirus associated molecular mimicry common to SARS-CoV-2 peptide Yekbun Adiguzela* aDepartment of Biophysics, School of Medicine, Altinbas University, Istanbul, Turkey *[email protected] Relationship of COVID-19 and immunity is complex and can involve autoimmune reactions through molecular mimicry. We investigated autoimmunity related pathological mechanisms involving molecular mimicry that are common to certain coronaviruses, including SARS-CoV-2, by means of a selected peptide sequence (CFLGYFCTCYFGLFC). Accordingly, coronavirus- associated sequences that are homologous to that 15mer sequence in the SARS- CoV-2 proteome are attained first. Then, homologous human and coronavirus sequences are obtained, wherein the coronavirus sequences are homologous to the 15mer SARS-CoV-2 peptide. All the identified query-subject sequences contained at least 7 residue matches in the aligned regions. Finally, parts of those coronavirus and host sequences, which are predicted to have high affinity to the same human leukocyte antigen (HLA) alleles as that of the SARS-CoV-2 sequence, are selected among the query and subject epitope-pairs that were both (predicted to be) strongly binding to the same HLA alleles. The proteins or the protein regions with those predicted epitopes include, but not limited to, immunoglobulin heavy chain junction regions, phospholipid phosphatase-related protein type 2, slit homolog 2 protein, and CRB1 isoform I precursor. These proteins are potentially associated with certain pathologies, but especially the possible CRB1 related coronavirus pathogenicity could be furthered by autoimmunity risk in HLA*A24:02 serotypes.
    [Show full text]
  • Molecular Mimicry Nervous System Autoimmune Disease by Induces
    The Journal of Immunology Viral Delivery of an Epitope from Haemophilus influenzae Induces Central Nervous System Autoimmune Disease by Molecular Mimicry1 J. Ludovic Croxford, Holly A. Anger, and Stephen D. Miller2 Multiple sclerosis (MS) is an autoimmune CNS demyelinating disease in which infection may be an important initiating factor. Pathogen-induced cross-activation of autoimmune T cells may occur by molecular mimicry. Infection with wild-type Theiler’s murine encephalomyelitis virus induces a late-onset, progressive T cell-mediated demyelinating disease, similar to MS. To deter- mine the potential of virus-induced autoimmunity by molecular mimicry, a nonpathogenic neurotropic Theiler’s murine enceph- alomyelitis virus variant was engineered to encode a mimic peptide from protease IV of Haemophilus influenzae (HI), sharing 6 of 13 aa with the dominant encephalitogenic proteolipid protein (PLP) epitope PLP139–151. Infection of SJL mice with the HI mimic-expressing virus induced a rapid-onset, nonprogressive paralytic disease characterized by potent activation of self-reactive ؉ PLP139–151-specific CD4 Th1 responses. In contrast, mice immunized with the HI mimic-peptide in CFA did not develop disease, ؉ associated with the failure to induce activation of PLP139–151-specific CD4 Th1 cells. However, preinfection with the mimic- expressing virus before mimic-peptide immunization led to severe disease. Therefore, infection with a mimic-expressing virus directly initiates organ-specific T cell-mediated autoimmunity, suggesting that pathogen-delivered innate immune signals may play a crucial role in triggering differentiation of pathogenic self-reactive responses. These results have important implications for explaining the pathogenesis of MS and other autoimmune diseases. The Journal of Immunology, 2005, 174: 907–917.
    [Show full text]
  • Molecular Mimicry May Contribute to Pathogenesis of Ulcerative Colitis
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector FEBS 29433 FEBS Letters 579 (2005) 2261–2266 Hypothesis Molecular mimicry may contribute to pathogenesis of ulcerative colitis Gopala Kovvali*, Kiron M. Das UMDNJ-Robert Wood Johnson Medical School, CrohnÕs and Colitis Center of New Jersey, New Brunswick, NJ 08903, United States Received 14 December 2004; revised 7 February 2005; accepted 15 February 2005 Available online 19 March 2005 Edited by Beat Imhof maintenance of fine balance of human immune system. An er- Abstract Ulcerative colitis (UC) is a chronic inflammatory bowel disease with mucosal inflammation and ulceration of the ror in judgment could lead to self-destruction of host cells. colon. There seems to be no single etiological factor responsible Infection with certain parasites, bacteria, viruses, mycobacte- for the onset of the disease. Autoimmunity has been emphasized ria, and yeast can potentially induce autoimmunity [2]. in the pathogenesis of UC. Perinuclear anti-neutrophil cytoplas- The concept of molecular mimicry states that antigenic mic antibodies (pANCA) are common in UC, and recently two determinants of infectious microorganisms resemble structures major species of proteins immunoreactive to pANCA were de- in the tissue of the host but differ enough to be recognized as tected in bacteria from the anaerobic libraries. This implicates foreign by the host immune system [1]. The initial support colonic bacterial protein as a possible trigger for the disease- for the suggestion that molecular mimicry might play a role associated immune response. Autoantibodies and T-cell response in autoimmune disease was found in 1983 when the antibody against human tropomyosin isoform 5 (hTM5), an isoform pre- against the phosphoprotein of measles virus and Herpes sim- dominantly expressed in colon epithelial cells, were demonstrated in patients with UC but not in CrohnÕs colitis.
    [Show full text]