Chapter 3 : Molecular Mimicry and Central Nervous System Autoimmune Disease

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

Molecular Mimicry and Central Nervous System Autoimmune Disease, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818074/9781555811945_Chap03-1.gif /docserver/preview/fulltext/10.1128/9781555818074/9781555811945_Chap03-2.gif


Infections have been associated with the initiation and/or exacerbation of multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS). It is suspected that tolerance to self-CNS antigens is broken by several linked events. This results in the initiation or induction of anti-CNS immune responses, which lead to inflammation and demyelination. Myelin basic protein (MBP) is a major component of CNS myelin, and when it is emulsified in adjuvant it can be used to induce experimental allergic encephalomyelitis (EAE) when it is injected into animals. Researchers found that 8 of 17 patients had lymphocytes that proliferated in response to MBP, whereas 6 of 40 individuals with measles without encephalomyelitis had such lymphocytes. Recently, other researchers extended the concept of molecular mimicry and autoimmune CNS disease. They have elegantly shown that the cross-reacting epitope between virus microbe and self-CNS protein does not need to have identical amino acids in order for T-cell recognition to occur. Theiler's murine encephalomyelitis virus (TMEV) infection of mice leads to a chronic demyelinating disease that has similarities to the human demyelinating disease MS. Early after infection natural killer (NK) cells can kill infected cells as part of the innate immune response. Viruses can cause direct lysis of infected cells through either apoptotic or necrotic pathways. Once an antiviral immune response develops, antiviral antibodies can bind to the surfaces of infected cells, leading to the activation of the complement cascade that eventually kills the infected cell.

Citation: Fujinami R. 2000. Molecular Mimicry and Central Nervous System Autoimmune Disease, p 27-38. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch3

Key Concept Ranking

Central Nervous System Diseases
Major Histocompatibility Complex
Theiler's Murine Encephalomyelitis
Lymphocytic choriomeningitis virus
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

Virus infection likely occurs in the periphery. Antigen-presenting cells (APCs) are infected and can present antigen in the MHC class I to CD8 T cells. In addition, antigen-presenting cells can ingest and process infected cell debris, leading to presentation of epitopes via class II and activation of CD4 T cells. Infected cells can be killed by several mechanisms. Virus can directly kill cells, leading to release of additional progeny virus. Activated NK cells can kill infected cells early after infection, leading to a reduction of virus progeny. As an immune response is mounted antibody and complement can kill infected cells. In many instances antibodies need to recognize the viral glycoproteins expressed on the surfaces of the infected cell. CD8 and, in some cases, CD4 T cells can lyse virus-infected cells through either perforin or Fas-mediated pathways. Ab, antibody; C, complement.

Citation: Fujinami R. 2000. Molecular Mimicry and Central Nervous System Autoimmune Disease, p 27-38. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch3
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Once CD4 or CD8 T cells are activated they can readily cross the blood-brain barrier. There these cells recognize common epitopes between virus and self-CNS antigens and release proinflammatory cytokines. Many of these are myelinotoxic and can kill the myelin-producing cell, the oligodendrocyte (OLIGO). In addition, macrophages (MAC) and plasma cells are drawn into the areas of inflammation. Plasma cells locally produce cross-reacting antibodies that bind to the myelin and/or myelin-supporting cells. Macrophages can recognize antibody produced by the plasma cells bound to myelin through Fc receptors. As myelin is eroded nerve conduction diminishes, leading to clinical signs of disease.

Citation: Fujinami R. 2000. Molecular Mimicry and Central Nervous System Autoimmune Disease, p 27-38. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch3
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Bahmanyar, S.,, J. Srinivasappa,, P. Casali,, R. S. Fujinami,, M. B. A. Oldstone,, and A. L. Notkins. 1987. Antigenic mimicry between measles virus and human T lymphocytes. J. Infect. Dis. 156:526527.
2. Barnett, L. A.,, and R. S. Fujinami,. 1997. Autoantigens of the nervous system, p. 333363. In R. W. Keane, and W. F. Hickey (ed.), Immunology of the Nervous System. Oxford University Press, New York, N.Y.
3. Barnett, L. A.,, J. L. Whitton,, Y. Wada,, and R. S. Fujinami. 1993. Enhancement of autoimmune disease using recombinant vaccinia virus encoding myelin proteolipid protein. J. Neuroimmunol. 44:1525.
4. Barnett, L. A.,, J. L. Whitton,, L. Y. Wang,, and R. S. Fujinami. 1996. Virus encoding an encephalitogenic peptide protects mice from experimental allergic encephalomyelitis. J. Neuroimmunol. 64:163173.
5. Damian, R. T. 1964. Molecular mimicry: antigen sharing by parasite and host and its consequences. Am. Nat. XCVIII:129149.
6. Damian, R. T., 1988. Parasites and molecular mimicry, p. 211. In Å. Lemmark,, T. Dyrberg,, L. Terenius,, and B. Hökfelt (ed.), Molecular Mimicry in Health and Disease. Elsevier Science Publishers B.V. (Biomedical Division), Amsterdam, The Netherlands.
7. Damian, R. T. 1989. Molecular mimicry: parasite evasion and host defense, Curr. Top. Microbiol. Immunol. 145:101115.
8. Dhib-Jalbut, S.,, and S. Jacobson. 1994. Cytotoxic T cells in paramyxovirus infection of humans. Curr. Top. Microbiol. Immunol. 189:109121.
9. Ebers, G. C.,, and D. A. Dyment. 1998. Genetics of multiple sclerosis. Semin. Neurol. 18:295299.
10. Edwards, S.,, M. Zvartau,, H. Clarke,, W. Irving,, and L. D. Blumhardt. 1998. Clinical relapses and disease activity on magnetic resonance imaging associated with viral upper respiratory tract infections in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 64:736741.
11. Evans, C. F.,, M. S. Horwitz,, M. V. Hobbs,, and M. B. A. Oldstone. 1996. Viral infection of transgenic mice expressing a viral protein in oligodendrocytes leads to chronic central nervous system autoimmune disease. J. Exp. Med. 184:23712384.
12. Fujinami, R. S.,, and M. B. A. Oldstone. 1985. Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science 230:10431045.
13. Fujinami, R. S.,, M. B. A. Oldstone,, Z. Wroblewska,, M. E. Frankel,, and H. Koprowski. 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 80:23452350.
14. Fujinami, R. S.,, A. Zurbriggen,, and H. C. Powell. 1988. Monoclonal antibody defines determinant between Theiler's virus and lipid-like structures. J. Neuroimmunol. 20:2532.
15. Genain, C. P.,, B. Cannella,, S. L. Hauser,, and C. S. Raine. 1999. Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nat. Med. 5:170175.
16. Gran, B.,, B. Hemmer,, and R. Martin. 1999. Molecular mimicry and multiple sclerosisùa possible role for degenerate T cell recognition in the induction of autoimmune responses. J. Neural Transm. Suppl. 55:1931.
17. Jacobson, S.,, J. R. Richert,, W. E. Biddison,, A. Satinsky,, R. J. Hartzman,, and H. F. McFarland. 1994. Measles virus-specific T4+ human cytotoxic T cell clones are restricted by class II HLA antigens. J. Immunol. 133:754757.
18. Johnson, R. T. 1994. The virology of demyelinating diseases. Ann. Neurol. 36(Suppl.):S54S60.
19. Johnson, R. T.,, D. E. Griffin,, R. L. Hirsch,, J. S. Wolinsky,, S. Roedenbeck,, I. Lindo-de-Soriano,, and A. Vaisberg. 1984. Measles encephalomyelitis—clinical and immunologic studies. N. Engl. J. Med. 310:137141.
20. Kies, M. W.,, R. E. Martenson,, and G. E. Deibler. 1972. Myelin basic proteins. Adv. Exp. Med. Biol. 32:201214.
21. Kurtzke, J. F. 1976. Multiple sclerosis among immigrants. Br. Med. J. 1:15271528.
22. Kurtzke, J. F. 1977. Geography in multiple sclerosis. J. Neurol. 215:126.
23. Kurtzke, J. F. 1993. Epidemiologic evidence for multiple sclerosis as an infection. Clin. Microbiol. Rev. 6:382427.
24. Kurtzke, J. F.,, L. T. Kurland,, and I. D. Goldberg. 1971. Mortality and migration in multiple sclerosis. Neurology 21:11861197.
25. Maatta, J. A.,, M. S. Kaldman,, S. Sakoda,, A. A. Salmi,, and A. E. Hinkkanen. 1999. Encephalitogenicity of myelin-associated oligodendrocytic basic protein and 2', 3'-cyclic nucleotide 3'-phosphodiesterase for BALB/c and SJL mice. Immunology 95:383388.
26. Marchalonis, J. J.,, S. F. Schluter,, L. Wilson,, D. E. Yocum,, J. T. Boyer,, and M. M. B. Kay. 1993. Natural human antibodies to synthetic peptide autoantigens: correlations with age and autoimmune disease. Gerontology 39:6579.
27. Metz, L. M.,, S. D. McGuinness,, and C. Harris. 1998. Urinary tract infections may trigger relapse in multiple sclerosis. Axon 19:6770.
28. Mokhtarian, F.,, Z. Zhang,, Y. Shi,, E. Gonzales,, and R. A. Sobel. 1999. Molecular mimicry between a viral peptide and a myelin oligodendrocyte glycoprotein peptide induces autoimmune demyelinating disease in mice. J. Neuroimmunol. 95:4354.
29. Oldstone, M. B. A.,, and F. J. Dixon. 1971. Immune complex disease in chronic viral infections. J. Exp. Med. 134:32l0s.
30. Pamer, E.,, and P. Cresswell. 1998. Mechanisms of MHC class I-restricted antigen processing. Annu. Rev. Immunol. 16:323358.
31. Rapp, N. S.,, J. Gilroy,, and A. M. Lerner. 1995. Role of bacterial infection in exacerbation of multiple sclerosis. Am. J. Phys. Med. Rehabil. 74:415418.
32. Rodman, T. C.,, S. E. To,, J. J. Sullivan,, and R. Winston. 1997. Innate natural antibodies. Primary roles indicated by specific epitopes. Hum. Immunol. 55:8795.
33. Rodriguez, F.,, L. L. An,, S. Harkins,, J. Zhang,, M. Yokoyama,, G. Widera,, J. T. Fuller,, C. Kincaid,, I. L. Campbell,, and J. L. Whitton. 1998. DNA immunization with minigenes: low frequency of memory cytotoxic T lymphocytes and inefficient antiviral protection are rectified by ubiquitination. J. Virol. 72:51745181.
34. Rodriguez, F.,, J. Zhang,, and J. L. Whitton. 1997. DNA immunization: ubiquitination of a viral protein enhances cytotoxic T-lymphocyte induction and antiviral protection but abrogates antibody induction. J. Virol. 71:84978503.
35. Ruiz, P. J.,, H. Garren,, I. U. Ruiz,, D. L. Hirschberg,, L.-V. T. Nguyen,, M. V. Karpuj,, M. T. Cooper,, D. J. Mitchell,, C. G. Fathman,, and L. Steinman. 1999. Suppressive immunization with DNA encoding a self-peptide prevents autoimmune disease: modulation of T cell costimulation. J. Immunol. 162:33363341.
36. Sibley, W. A.,, C. R. Bamford,, and K. Clark. 1985. Clinical viral infections and multiple sclerosis. Lancet 1:13131315.
37. Spalter, S. H.,, S. V. Kaveri,, E. Bonnin,, J. C. Mani,, J. P. Cartron,, and M. D. Kazatchkine. 1999. Normal human serum contains natural antibodies reactive with autologous ABO blood group antigens. Blood 93:44184424.
38. Srinivasappa, J.,, J. Saegusa,, B. S. Prabhakar,, M. K. Gentry,, M. Buchmeier,, T. J. Wiktor,, H. Koprowski,, M. B. A. Oldstone,, and A. L. Notkins. 1986. Molecular mimicry: frequency of reactivity of monoclonal antiviral antibodies with normal tissues. J. Virol. 57:397401.
39. Stevens, D. B.,, K. Chen,, R. S. Seitz,, E. E. Sercarz,, and J. M. Bronstein. 1999. Oligodendrocyte-specific protein peptides induce experimental autoimmune encephalomyelitis in SJL/J mice. J. Immunol. 162:75017509.
40. Talbot, P. J.,, J. S. Paquette,, C. Ciurli,, J. P. Antel,, and F. Ouellet. 1996. Myelin basic protein and human coronavirus 229E cross-reactive T cells in multiple sclerosis. Ann. Neurol. 39:233240.
41. Tsunoda, I.,, L.-Q. Kuang,, N. D. Tolley,, J. L. Whitton,, and R. S. Fujinami. 1998. Enhancement of experimental allergic encephalomyelitis (EAE) by DNA immunization with myelin proteolipid protein (PLP) plasmid DNA. J. Neuropathol. Exp. Neurol. 57:758767.
42. Tsunoda, I.,, N. D. Tolley,, D. J. Theil,, J. L. Whitton,, H. Kobayashi,, and R. S. Fujinami. 1999. Exacerbation of viral and autoimmune animal models for multiple sclerosis by bacterial DNA. Brain Pathol. 9:481493.
43. van Binnendijk, R. S.,, M. C. Poelen,, K. C. Kuijpers,, A. D. Osterhaus,, and F. G. Uytdehaag. 1990. The predominance of CD8+ T cells after infection with measles virus suggests a role for CD8+ class I MHC-restricted cytotoxic T lymphocytes (CTL) in recovery from measles. Clonal analyses of human CD8+ class I MHC-restricted CTL. J. Immunol. 144:23942399.
44. Ward, B. J.,, R. T. Johnson,, A. Vaisberg,, E. Jauregui,, and D. E. Griffin. 1990. Spontaneous proliferation of peripheral mononuclear cells in natural measles virus infection: identification of dividing cells and correlation with mitogen responsiveness. Clin. Immunol. Immunopathol. 55:315326.
45. Whitton, J. L.,, F. Rodriguez,, J. Zhang,, and D. E. Hassett. 1999. DNA immunization: mechanistic studies. Vaccine 17:16121619.
46. Yamada, M.,, A. Zurbriggen,, M. B. A. Oldstone,, and R. S. Fujinami. 1991. Common immunologic determinant between human immunodeficiency virus type I gp41 and astrocytes. J. Virol. 65:13701376.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error