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Clinical Reviews in Allergy & Immunology
Published in: Clinical Reviews in Allergy & Immunology 1/2012

01-02-2012

Molecular Mimicry as a Mechanism of Autoimmune Disease

Authors: Matthew F. Cusick, Jane E. Libbey, Robert S. Fujinami

Published in: Clinical Reviews in Allergy & Immunology | Issue 1/2012

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Abstract

A variety of mechanisms have been suggested as the means by which infections can initiate and/or exacerbate autoimmune diseases. One mechanism is molecular mimicry, where a foreign antigen shares sequence or structural similarities with self-antigens. Molecular mimicry has typically been characterized on an antibody or T cell level. However, structural relatedness between pathogen and self does not account for T cell activation in a number of autoimmune diseases. A proposed mechanism that could have been misinterpreted for molecular mimicry is the expression of dual T cell receptors (TCR) on a single T cell. These T cells have dual reactivity to both foreign and self-antigens leaving the host vulnerable to foreign insults capable of triggering an autoimmune response. In this review, we briefly discuss what is known about molecular mimicry followed by a discussion of the current understanding of dual TCRs. Finally, we discuss three mechanisms, including molecular mimicry, dual TCRs, and chimeric TCRs, by which dual reactivity of the T cell may play a role in autoimmune diseases.
Literature
1.
Abou-Raya A, Abou-Raya S (2006) Inflammation: a pivotal link between autoimmune diseases and atherosclerosis. Autoimmun Rev 5:331–337PubMed
2.
Selgrade MK, Cooper GS, Germolec DR, Heindel JJ (1999) Linking environmental agents and autoimmune disease: an agenda for future research. Environ Health Perspect 107(Suppl 5):811–813PubMedPubMedCentral
3.
von Herrath MG, Fujinami RS, Whitton JL (2003) Microorganisms and autoimmunity: making the barren field fertile? Nat Rev Microbiol 1:151–157
4.
5.
Fujinami RS (2001) Viruses and autoimmune disease—two sides of the same coin? Trends Microbiol 9:377–381PubMed
6.
Ascherio A, Munger KL (2007) Environmental risk factors for multiple sclerosis. Part II: noninfectious factors. Ann Neurol 61:504–513PubMed
7.
McCoy L, Tsunoda I, Fujinami RS (2006) Multiple sclerosis and virus induced immune responses: autoimmunity can be primed by molecular mimicry and augmented by bystander activation. Autoimmunity 39:9–19PubMed
8.
Sfriso P, Ghirardello A, Botsios C et al (2010) Infections and autoimmunity: the multifaceted relationship. J Leukoc Biol 87:385–395PubMed
9.
10.
Iwakura Y, Ishigame H, Saijo S, Nakae S (2011) Functional specialization of interleukin-17 family members. Immunity 34:149–162PubMed
11.
Libbey JE, McCoy LL, Fujinami RS (2007) Molecular mimicry in multiple sclerosis. Int Rev Neurobiol 79:127–147PubMed
12.
Whitton JL, Feuer R (2004) Myocarditis, microbes and autoimmunity. Autoimmunity 37:375–386PubMed
13.
Libbey JE, Fujinami RS (2010) Role for antibodies in altering behavior and movement. Autism Res 3:147–152PubMed
14.
Shahrizaila N, Yuki N (2011) Guillain–Barré syndrome animal model: the first proof of molecular mimicry in human autoimmune disorder. J Biomed Biotechnol 2011:829129PubMedPubMedCentral
15.
Ahmed R (1992) Immunological memory against viruses. Semin Immunol 4:105–109PubMed
16.
Fujinami RS, Oldstone MBA (1985) Amino acid homology between the encephalitogenic site of myelin basic protein and virus: Mechanism for autoimmunity. Science 230:1043–1045PubMed
17.
Oldstone MBA (1987) Molecular mimicry and autoimmune disease. Cell 50:819–820PubMed
18.
Fujinami RS, Oldstone MBA, Wroblewska Z, Frankel ME, Koprowski H (1983) Molecular mimicry in virus infection: crossreaction of measles virus phosphoprotein or of herpes simplex virus protein with human intermediate filaments. Proc Natl Acad Sci USA 80:2346–2350PubMed
19.
McRae BL, Vanderlugt CL, Dal Canto MC, Miller SD (1995) Functional evidence for epitope spreading in the relapsing pathology of experimental autoimmune encephalomyelitis. J Exp Med 182:75–85PubMed
20.
Vanderlugt CL, Begolka WS, Neville KL et al (1998) The functional significance of epitope spreading and its regulation by co-stimulatory molecules. Immunol Rev 164:63–72PubMed
21.
Scherer MT, Ignatowicz L, Winslow GM, Kappler JW, Marrack P (1993) Superantigens: Bacterial and viral proteins that manipulate the immune system. Annu Rev Cell Biol 9:101–128PubMed
22.
Chen HD, Fraire AE, Joris I, Brehm MA, Welsh RM, Selin LK (2001) Memory CD8+ T cells in heterologous antiviral immunity and immunopathology in the lung. Nat Immunol 2:1067–1076PubMed
23.
Zabriskie JB, Freimer EH (1966) An immunological relationship between the group A streptococcus and mammalian muscle. J Exp Med 124:661–678PubMedPubMedCentral
24.
Gregersen PK, Silver J, Winchester RJ (1987) The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 30:1205–1213PubMed
25.
Burns J, Rosenzweig A, Zweiman B, Lisak RP (1983) Isolation of myelin basic protein-reactive T-cell lines from normal human blood. Cell Immunol 81:435–440PubMed
26.
Mathis D, Vence L, Benoist C (2001) β-Cell death during progression to diabetes. Nature 414:792–798PubMed
27.
Tisch R, McDevitt H (1996) Insulin-dependent diabetes mellitus. Cell 85:291–297PubMed
28.
Bertsias GK, Salmon JE, Boumpas DT (2010) Therapeutic opportunities in systemic lupus erythematosus: state of the art and prospects for the new decade. Ann Rheum Dis 69:1603–1611PubMed
29.
Ebringer A, Baines M, Ptaszynska T (1985) Spondyloarthritis, uveitis, HLA-B27 and Klebsiella. Immunol Rev 86:101–116PubMed
30.
Quaratino S, Thorpe CJ, Travers PJ, Londei M (1995) Similar antigenic surfaces, rather than sequence homology, dictate T-cell epitope molecular mimicry. Proc Natl Acad Sci USA 92:10398–10402PubMed
31.
Wandinger K-P, Jabs W, Siekhaus A et al (2000) Association between clinical disease activity and Epstein–Barr virus reactivation in MS. Neurology 55:178–184PubMed
32.
Sinigaglia F, Hammer J (1994) Defining rules for the peptide–MHC class II interaction. Curr Opin Immunol 6:52–56PubMed
33.
Wucherpfennig KW, Sette A, Southwood S et al (1994) Structural requirements for binding of an immunodominant myelin basic protein peptide to DR2 isotypes and for its recognition by human T cell clones. J Exp Med 179:279–290PubMed
34.
Reay PA, Kantor RM, Davis MM (1994) Use of global amino acid replacements to define the requirements for MHC binding and T cell recognition of moth cytochrome c (93–103). J Immunol 152:3946–3957PubMed
35.
Wucherpfennig KW, Strominger JL (1995) Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 80:695–705PubMed
36.
Hausmann S, Martin M, Gauthier L, Wucherpfennig KW (1999) Structural features of autoreactive TCR that determine the degree of degeneracy in peptide recognition. J Immunol 162:338–344PubMed
37.
Wucherpfennig KW, Allen PM, Celada F et al (2007) Polyspecificity of T cell and B cell receptor recognition. Semin Immunol 19:216–224PubMedPubMedCentral
38.
Theil DJ, Tsunoda I, Rodriguez F, Whitton JL, Fujinami RS (2001) Viruses can silently prime for and trigger central nervous system autoimmune disease. J Neurovirol 7:220–227PubMed
39.
Tsunoda I, Libbey JE, Fujinami RS (2007) Sequential polymicrobial infections lead to CNS inflammatory disease: possible involvement of bystander activation in heterologous immunity. J Neuroimmunol 188:22–33PubMedPubMedCentral
40.
Ohashi PS, Oehen S, Buerki K et al (1991) Ablation of “tolerance” and induction of diabetes by virus infection in viral antigen transgenic mice. Cell 65:305–317PubMed
41.
Oldstone MBA, Nerenberg M, Southern P, Price J, Lewicki H (1991) Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response. Cell 65:319–331PubMed
42.
Petrie HT, Livak F, Schatz DG, Strasser A, Crispe IN, Shortman K (1993) Multiple rearrangements in T cell receptor α chain genes maximize the production of useful thymocytes. J Exp Med 178:615–622PubMed
43.
Pang SS, Berry R, Chen Z et al (2010) The structural basis for autonomous dimerization of the pre-T-cell antigen receptor. Nature 467:844–848PubMed
44.
Casanova J-L, Romero P, Widmann C, Kourilsky P, Maryanski JL (1991) T cell receptor genes in a series of class I major histocompatibility complex-restricted cytotoxic T lymphocyte clones specific for a Plasmodium berghei nonapeptide: implications for T cell allelic exclusion and antigen-specific repertoire. J Exp Med 174:1371–1383PubMed
45.
Padovan E, Casorati G, Dellabona P, Meyer S, Brockhaus M, Lanzavecchia A (1993) Expression of two T cell receptor α chains: dual receptor T cells. Science 262:422–424PubMed
46.
Corthay A, Nandakumar KS, Holmdahl R (2001) Evaluation of the percentage of peripheral T cells with two different T cell receptor α-chains and of their potential role in autoimmunity. J Autoimmun 16:423–429PubMed
47.
Davodeau F, Peyrat M-A, Romagné F et al (1995) Dual T cell receptor β chain expression on human T lymphocytes. J Exp Med 181:1391–1398PubMed
48.
Padovan E, Giachino C, Cella M, Valitutti S, Acuto O, Lanzavecchia A (1995) Normal T lymphocytes can express two different T cell receptor β chains: implications for the mechanism of allelic exclusion. J Exp Med 181:1587–1591PubMed
49.
Munthe LA, Blichfeldt E, Sollien A, Dembic Z, Bogen B (1996) T cells with two Tcrβ chains and reactivity to both MHC/idiotypic peptide and superantigen. Cell Immunol 170:283–290PubMed
50.
Alam SM, Crispe IN, Gascoigne NR (1995) Allelic exclusion of mouse T cell receptor α chains occurs at the time of thymocyte TCR up-regulation. Immunity 3:449–458PubMed
51.
Marolleau J-P, Fondell JD, Malissen M et al (1988) The joining of germ-line Vα to Jα genes replaces the preexisting Vα-Jα complexes in a T cell receptor α, β positive T cell line. Cell 55:291–300PubMed
52.
Malissen M, Trucy J, Letourneur F et al (1988) A T cell clone expresses two T cell receptor α genes but uses one αβ heterodimer for allorecognition and self MHC-restricted antigen recognition. Cell 55:49–59PubMed
53.
Saito T, Sussman JL, Ashwell JD, Germain RN (1989) Marked differences in the efficiency of expression of distinct αβ T cell receptor heterodimers. J Immunol 143:3379–3384PubMed
54.
Vacchio MS, Granger L, Kanagawa O et al (1993) T cell receptor Vα-Vβ combinatorial selection in the expressed T cell repertoire. J Immunol 151:1322–1327PubMed
55.
Morris GP, Allen PM (2009) Cutting edge: highly alloreactive dual TCR T cells play a dominant role in graft-versus-host disease. J Immunol 182:6639–6643PubMedPubMedCentral
56.
Taupin J-L, Halary F, Dechanet J et al (1999) An enlarged subpopulation of T lymphocytes bearing two distinct γδ TCR in an HIV-positive patient. Int Immunol 11:545–552PubMed
57.
Söderström K, Bucht A, Halapi E, Grönberg A, Magnusson I, Kiessling R (1996) Increased frequency of abnormal γδ T cells in blood of patients with inflammatory bowel diseases. J Immunol 156:2331–2339PubMed
58.
Hinz T, Marx S, Nerl C, Kabelitz D (1996) Clonal expansion of γδ T cells expressing two distinct T-cell receptors. Br J Haematol 94:62–64PubMed
59.
Boehrer S, Hinz T, Schui D et al (2001) T-large granular lymphocyte leukaemia with natural killer cell-like cytotoxicity and expression of two different α-and β-T-cell receptor chains. Br J Haematol 112:201–203PubMed
60.
Weidmann E, Hinz T, Klein S et al (2000) Cytotoxic hepatosplenic γδ T-cell lymphoma following acute myeloid leukemia bearing two distinct γ chains of the T-cell receptor. Biologic and clinical features. Haematologica 85:1024–1031PubMed
61.
Ji Q, Perchellet A, Goverman JM (2010) Viral infection triggers central nervous system autoimmunity via activation of CD8+ T cells expressing dual TCRs. Nat Immunol 11:628–634PubMedPubMedCentral
62.
Blichfeldt E, Munthe LA, Rotnes JS, Bogen B (1996) Dual T cell receptor T cells have a decreased sensitivity to physiological ligands due to reduced density of each T cell receptor. Eur J Immunol 26:2876–2884PubMed
63.
Sarukhan A, Lanoue A, Franzke A, Brousse N, Buer J, von Boehmer H (1998) Changes in function of antigen-specific lymphocytes correlating with progression towards diabetes in a transgenic model. EMBO J 17:71–80PubMed
64.
Sarukhan A, Garcia C, Lanoue A, von Boehmer H (1998) Allelic inclusion of T cell receptor α genes poses an autoimmune hazard due to low-level expression of autospecific receptors. Immunity 8:563–570PubMed
65.
Tsunoda I, Kuang L-Q, Kobayashi-Warren M, Fujinami RS (2005) Central nervous system pathology caused by autoreactive CD8+ T cell clones following virus infection. J Virol 79:14640–14646PubMedPubMedCentral
66.
Perchellet A, Stromnes I, Pang JM, Goverman J (2004) CD8+ T cells maintain tolerance to myelin basic protein by ‘epitope theft’. Nat Immunol 5:606–614PubMed
67.
Borgulya P, Kishi H, Uematsu Y, von Boehmer H (1992) Exclusion and inclusion of α and β T cell receptor alleles. Cell 69:529–537PubMed
68.
Balomenos D, Balderas RS, Mulvany KP, Kaye J, Kono DH, Theofilopoulos AN (1995) Incomplete T cell receptor Vβ allelic exclusion and dual Vβ-expressing cells. J Immunol 155:3308–3312PubMed
69.
Hurst SD, Sitterding SM, Ji S, Barrett TA (1997) Functional differentiation of T cells in the intestine of T cell receptor transgenic mice. Proc Natl Acad Sci USA 94:3920–3925PubMed
70.
Heath WR, Miller JFAP (1993) Expression of two α chains on the surface of T cells in T cell receptor transgenic mice. J Exp Med 178:1807–1811PubMed
71.
Stagg AJ, Breban M, Hammer RE, Knight SC, Taurog JD (1995) Defective dendritic cell (DC) function in a HLA-B27 transgenic rat model of spondyloarthropathy (SpA). Adv Exp Med Biol 378:557–559PubMed
72.
Ebringer R, Cawdell D, Ebringer A (1979) Klebsiella pneumoniae and acute anterior uveitis in ankylosing spondylitis. Br Med J 1:383PubMedPubMedCentral
73.
Schwimmbeck PL, Yu DTY, Oldstone MBA (1987) Autoantibodies to HLA B27 in the sera of HLA B27 patients with ankylosing spondylitis and Reiter’s syndrome. Molecular mimicry with Klebsiella pneumoniae as potential mechanism of autoimmune disease. J Exp Med 166:173–181PubMed
74.
Shoenfeld Y, Blank M, Cervera R, Font J, Raschi E, Meroni PL (2006) Infectious origin of the antiphospholipid syndrome. Ann Rheum Dis 65:2–6PubMed
75.
Amedei A, Bergman MP, Appelmelk BJ et al (2003) Molecular mimicry between Helicobacter pylori antigens and H+, K+–adenosine triphosphatase in human gastric autoimmunity. J Exp Med 198:1147–1156PubMedPubMedCentral
76.
Lunardi C, Bason C, Leandri M et al (2002) Autoantibodies to inner ear and endothelial antigens in Cogan’s syndrome. Lancet 360:915–921PubMed
77.
Takahashi T, Yujiri T, Shinohara K et al (2004) Molecular mimicry by Helicobacter pylori CagA protein may be involved in the pathogenesis of H. pylori-associated chronic idiopathic thrombocytopenic purpura. Br J Haematol 124:91–96PubMed
78.
Direskeneli H, Hasan A, Shinnick T et al (1996) Recognition of B-cell epitopes of the 65 kDa HSP in Behçet’s disease. Scand J Immunol 43:464–471PubMed
79.
de Smet MD, Ramadan A (2001) Circulating antibodies to inducible heat shock protein 70 in patients with uveitis. Ocul Immunol Inflamm 9:85–92PubMed
80.
Suzuki Y, Hoshi K, Matsuda T, Mizushima Y (1992) Increased peripheral blood γδ+ T cells and natural killer cells in Behçet’s disease. J Rheumatol 19:588–592PubMed
81.
Mahesh SP, Li Z, Buggage R et al (2005) Alpha tropomyosin as a self-antigen in patients with Behçet’s disease. Clin Exp Immunol 140:368–375PubMedPubMedCentral
82.
de Smet MD, Dayan M (2000) Prospective determination of T-cell responses to S-antigen in Behçet’s disease patients and controls. Invest Ophthalmol Vis Sci 41:3480–3484PubMed
83.
Cunningham MW (2004) T cell mimicry in inflammatory heart disease. Mol Immunol 40:1121–1127PubMed
84.
Dieterich W, Ehnis T, Bauer M et al (1997) Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 3:797–801PubMed
85.
Plot L, Amital H (2009) Infectious associations of Celiac disease. Autoimmun Rev 8:316–319PubMed
86.
Iwai LK, Juliano MA, Juliano L, Kalil J, Cunha-Neto E (2005) T-cell molecular mimicry in Chagas disease: identification and partial structural analysis of multiple cross-reactive epitopes between Trypanosoma cruzi B13 and cardiac myosin heavy chain. J Autoimmun 24:111–117PubMed
87.
Cunha-Neto E, Bilate AM, Hyland KV, Fonseca SG, Kalil J, Engman DM (2006) Induction of cardiac autoimmunity in Chagas heart disease: a case for molecular mimicry. Autoimmunity 39:41–54PubMed
88.
Weiss MD, Luciano CA, Semino-Mora C, Dalakas MC, Quarles RH (1998) Molecular mimicry in chronic inflammatory demyelinating polyneuropathy and melanoma. Neurology 51:1738–1741PubMed
89.
Köller H, Kieseier BC, Jander S, Hartung H-P (2005) Chronic inflammatory demyelinating polyneuropathy. N Engl J Med 352:1343–1356PubMed
90.
Klasen IS, Melief MJ, van Halteren AGS et al (1994) The presence of peptidoglycan–polysaccharide complexes in the bowel wall and the cellular responses to these complexes in Crohn’s disease. Clin Immunol Immunopathol 71:303–308PubMed
91.
Massa M, Costouros N, Mazzoli F et al (2002) Self epitopes shared between human skeletal myosin and Streptococcus pyogenes M5 protein are targets of immune responses in active juvenile dermatomyositis. Arthritis Rheum 46:3015–3025PubMed
92.
De Re V, Sansonno D, Simula MP et al (2006) HCV-NS3 and IgG-Fc crossreactive IgM in patients with type II mixed cryoglobulinemia and B-cell clonal proliferations. Leukemia 20:1145–1154PubMed
93.
Yuki N, Tagawa Y, Handa S (1996) Autoantibodies to peripheral nerve glycosphingolipids SPG, SLPG, and SGPG in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. J Neuroimmunol 70:1–6PubMed
94.
Atkinson MA, Bowman MA, Campbell L, Darrow BL, Kaufman DL, Maclaren NK (1994) Cellular immunity to a determinant common to glutamate decarboxylase and coxsackie virus in insulin-dependent diabetes. J Clin Invest 94:2125–2129PubMedPubMedCentral
95.
Kaufman DL, Erlander MG, Clare-Salzler M, Atkinson MA, Maclaren NK, Tobin AJ (1992) Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent diabetes mellitus. J Clin Invest 89:283–292PubMedPubMedCentral
96.
Ou D, Mitchell LA, Metzger DL, Gillam S, Tingle AJ (2000) Cross-reactive rubella virus and glutamic acid decarboxylase (65 and 67) protein determinants recognised by T cells of patients with type I diabetes mellitus. Diabetologia 43:750–762PubMed
97.
van der Werf N, Kroese FGM, Rozing J, Hillebrands J-L (2007) Viral infections as potential triggers of type 1 diabetes. Diabetes Metab Res Rev 23:169–183PubMed
98.
Baum H, Brusic V, Choudhuri K, Cunningham P, Vergani D, Peakman M (1995) MHC molecular mimicry in diabetes. Nat Med 1:388PubMed
99.
Jones DB, Armstrong NW (1995) Coxsackie virus and diabetes revisited. Nat Med 1:284PubMed
100.
Endl J, Otto H, Jung G et al (1997) Identification of naturally processed T cell epitopes from glutamic acid decarboxylase presented in the context of HLA-DR alleles by T lymphocytes of recent onset IDDM patients. J Clin Invest 99:2405–2415PubMedPubMedCentral
101.
McClain MT, Heinlen LD, Dennis GJ, Roebuck J, Harley JB, James JA (2005) Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry. Nat Med 11:85–89PubMed
102.
Fujinami RS, von Herrath MG, Christen U, Whitton JL (2006) Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease. Clin Microbiol Rev 19:80–94PubMedPubMedCentral
103.
Baum H (1995) Mitochondrial antigens, molecular mimicry and autoimmune disease. Biochim Biophys Acta 1271:111–121PubMed
104.
Shimoda S, Nakamura M, Ishibashi H et al (2003) Molecular mimicry of mitochondrial and nuclear autoantigens in primary biliary cirrhosis. Gastroenterology 124:1915–1925PubMed
105.
Kita H, Matsumura S, He X-S et al (2002) Analysis of TCR antagonism and molecular mimicry of an HLA-A*0201-restricted CTL epitope in primary biliary cirrhosis. Hepatology 36:918–926PubMed
106.
Selmi C, Bowlus CL, Gershwin ME, Coppel RL (2011) Primary biliary cirrhosis. Lancet 377:1600–1609PubMed
107.
Bogdanos D-P, Baum H, Grasso A et al (2004) Microbial mimics are major targets of crossreactivity with human pyruvate dehydrogenase in primary biliary cirrhosis. J Hepatol 40:31–39PubMed
108.
Johnston A, Gudjonsson JE, Sigmundsdottir H, Love TJ, Valdimarsson H (2004) Peripheral blood T cell responses to keratin peptides that share sequences with streptococcal M proteins are largely restricted to skin-homing CD8+ T cells. Clin Exp Immunol 138:83–93PubMedPubMedCentral
109.
Brandt ER, Yarwood PJ, McMillan DJ et al (2001) Antibody levels to the class I and II epitopes of the M protein and myosin are related to group A streptococcal exposure in endemic populations. Int Immunol 13:1335–1343PubMed
110.
Cunningham MW, McCormack JM, Talaber LR et al (1988) Human monoclonal antibodies reactive with antigens of the group A Streptococcus and human heart. J Immunol 141:2760–2766PubMed
111.
Adderson EE, Shikhman AR, Ward KE, Cunningham MW (1998) Molecular analysis of polyreactive monoclonal antibodies from rheumatic carditis: human anti-N-acetylglucosamine/anti-myosin antibody V region genes. J Immunol 161:2020–2031PubMed
112.
Rogers SW, Andrews PI, Gahring LC et al (1994) Autoantibodies to glutamate receptor GluR3 in Rasmussen’s encephalitis. Science 265:648–651PubMed
113.
McNamara JO, Patel M, He XP, Janumpalli S, Whitney KD (1996) Glutamate receptor autoimmunity in Rasmussen’s encephalitis. Cold Spring Harb Symp Quant Biol 61:327–332PubMed
114.
Hemachudha T, Griffin DE, Giffels JJ, Johnson RT, Moser AB, Phanuphak P (1987) Myelin basic protein as an encephalitogen in encephalomyelitis and polyneuritis following rabies vaccination. N Engl J Med 316:369–374PubMed
115.
Johnson RT, Griffin DE, Hirsch RL et al (1984) Measles encephalomyelitis—clinical and immunologic studies. N Engl J Med 310:137–141PubMed
116.
Tenembaum S, Chitnis T, Ness J, Hahn JS (2007) Acute disseminated encephalomyelitis. Neurology 68(Suppl 2):S23–S36PubMed
117.
Schwimmbeck PL, Dyrberg T, Drachman DB, Oldstone MBA (1989) Molecular mimicry and myasthenia gravis. An autoantigenic site of the acetylcholine receptor α-subunit that has biologic activity and reacts immunochemically with herpes simplex virus. J Clin Invest 84:1174–1180PubMedPubMedCentral
118.
Fujinami RS, Nelson JA, Walker L, Oldstone MBA (1988) Sequence homology and immunologic cross-reactivity of human cytomegalovirus with HLA-DR β chain: a means for graft rejection and immunosuppression. J Virol 62:100–105PubMedPubMedCentral
119.
Nauclér CS, Larsson S, Möller E (1996) A novel mechanism for virus-induced autoimmunity in humans. Immunol Rev 152:175–192PubMed
120.
Zhao Z-S, Granucci F, Yeh L, Schaffer PA, Cantor H (1998) Molecular mimicry by herpes simplex virus-type 1: autoimmune disease after viral infection. Science 279:1344–1347PubMed
121.
Gross DM, Forsthuber T, Tary-Lehmann M et al (1998) Identification of LFA-1 as a candidate autoantigen in treatment-resistant Lyme arthritis. Science 281:703–706PubMed
122.
Kirvan CA, Swedo SE, Heuser JS, Cunningham MW (2003) Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nat Med 9:914–920PubMed
123.
Kirvan CA, Cox CJ, Swedo SE, Cunningham MW (2007) Tubulin is a neuronal target of autoantibodies in Sydenham’s chorea. J Immunol 178:7412–7421PubMed
124.
Thurau SR, Diedrichs-Möhring M, Fricke H, Arbogast S, Wildner G (1997) Molecular mimicry as a therapeutic approach for an autoimmune disease: oral treatment of uveitis-patients with an MHC-peptide crossreactive with autoantigen—first results. Immunol Lett 57:193–201PubMed
125.
Lunardi C, Bason C, Navone R et al (2000) Systemic sclerosis immunoglobulin G autoantibodies bind the human cytomegalovirus late protein UL94 and induce apoptosis in human endothelial cells. Nat Med 6:1183–1186PubMed
126.
Lunardi C, Dolcino M, Peterlana D et al (2006) Antibodies against human cytomegalovirus in the pathogenesis of systemic sclerosis: a gene array approach. PLoS Med 3:e2PubMedPubMedCentral
127.
Stathopoulou EA, Routsias JG, Stea EA, Moutsopoulos HM, Tzioufas AG (2005) Cross-reaction between antibodies to the major epitope of Ro60 kD autoantigen and a homologous peptide of Coxsackie virus 2B protein. Clin Exp Immunol 141:148–154PubMedPubMedCentral
128.
Hiemstra HS, Schloot NC, van Veelen PA et al (2001) Cytomegalovirus in autoimmunity: T cell crossreactivity to viral antigen and autoantigen glutamic acid decarboxylase. Proc Natl Acad Sci USA 98:3988–3991PubMed
129.
Ali F, Rowley M, Jayakrishnan B, Teuber S, Gershwin ME, Mackay IR (2011) Stiff-person syndrome (SPS) and anti-GAD-related CNS degenerations: protean additions to the autoimmune central neuropathies. J Autoimmun 37:79–87PubMed
130.
Appelmelk BJ, Simoons-Smit I, Negrini R et al (1996) Potential role of molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in autoimmunity. Infect Immun 64:2031–2040PubMedPubMedCentral
131.
Sohn S, Lee ES, Bang D, Lee S (1998) Behcet’s disease-like symptoms induced by the Herpes simplex virus in ICR mice. Eur J Dermatol 8:21–23PubMed
132.
Lawson CM, O’Donoghue HL, Reed WD (1992) Mouse cytomegalovirus infection induces antibodies which cross-react with virus and cardiac myosin: A model for the study of molecular mimicry in the pathogenesis of viral myocarditis. Immunology 75:513–519PubMed
133.
Christen U, Edelmann KH, McGavern DB et al (2004) A viral epitope that mimics a self antigen can accelerate but not initiate autoimmune diabetes. J Clin Invest 114:1290–1298PubMedPubMedCentral
134.
Watanabe K, Kim S, Nishiguchi M, Suzuki H, Watarai M (2005) Brucella melitensis infection associated with Guillain-Barré syndrome through molecular mimicry of host structures. FEMS Immunol Med Microbiol 45:121–127PubMed
135.
Hintermann E, Holdener M, Bayer M et al (2011) Epitope spreading of the anti-CYP2D6 antibody response in patients with autoimmune hepatitis and in the CYP2D6 mouse model. J Autoimmun 37:242–253
136.
Holdener M, Hintermann E, Bayer M et al (2008) Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection. J Exp Med 205:1409–1422PubMedPubMedCentral
137.
Avery AC, Zhao Z-S, Rodriguez A et al (1995) Resistance to herpes stromal keratitis conferred by an IgG2a-derived peptide. Nature 376:431–434PubMed
138.
de Smet MD, Chan CC (2001) Regulation of ocular inflammation—what experimental and human studies have taught us. Prog Retin Eye Res 20:761–797PubMed
139.
Shen DF, Chang MA, Matteson DM, Buggage R, Kozhich AT, Chan CC (2000) Biphasic ocular inflammatory response to endotoxin-induced uveitis in the mouse. Arch Ophthalmol 118:521–527PubMed
140.
Fleck M, Kern ER, Zhou T, Lang B, Mountz JD (1998) Murine cytomegalovirus induces a Sjögren’s syndrome-like disease in C57Bl/6-lpr/lpr mice. Arthritis Rheum 41:2175–2184PubMed
141.
Yamada M, Zurbriggen A, Fujinami RS (1990) Monoclonal antibody to Theiler’s murine encephalomyelitis virus defines a determinant on myelin and oligodendrocytes, and augments demyelination in experimental allergic encephalomyelitis. J Exp Med 171:1893–1907PubMed
142.
Mokhtarian F, Zhang Z, Shi Y, Gonzales E, Sobel RA (1999) Molecular mimicry between a viral peptide and a myelin oligodendrocyte glycoprotein peptide induces autoimmune demyelinating disease in mice. J Neuroimmunol 95:43–54PubMed
Metadata
Title
Molecular Mimicry as a Mechanism of Autoimmune Disease
Authors
Matthew F. Cusick
Jane E. Libbey
Robert S. Fujinami
Publication date
01-02-2012
Publisher
Humana Press Inc
Published in
Clinical Reviews in Allergy & Immunology / Issue 1/2012
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI
https://doi.org/10.1007/s12016-011-8294-7

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