Chapter 2 : Principles of Molecular Mimicry and Autoimmune Disease

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The role of molecular mimicry in the host-parasite relationship is complex, and different investigators may have different ideas in mind when they consider the subject. The aim is to examine the immunological principles behind the phenomenon of host-parasite mimicry and autoimmune disease. Antigen recognition, including self-recognition, requires pre-existing T cells and B cells that bear antigen receptors complementary to the antigen, be it a foreign antigen or a self-antigen; this is the basic tenet of the clonal selection theory of acquired immunity. So, an autoimmune disease would not be possible unless autoimmune lymphocytes preceded the outbreak of the disease. If rodents and humans feature immunological homunculi, then the positive selection of strong autoimmunity to at least some self-antigens has been conserved during evolution and so is likely to be advantageous. The classical formulation of the theory taught that immune specificity was achieved automatically. Macrophages, T cells, and B cells each sense a unique aspect of the immune encounter, and, at the same time, these cells mutually exchange information (by way of cytokines, chemokines, antibodies, and other cell interaction molecules) that is obtained from their different views. To induce an autoimmune disease, an infectious agent must activate physiological autoimmunity unnaturally. The potential for mimicry inherent in the evolution and coevolution of hosts and parasites is compounded by the intrinsic degeneracy of biological receptors.

Citation: Cohen I. 2000. Principles of Molecular Mimicry and Autoimmune Disease, p 17-26. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch2

Key Concept Ranking

Adaptive Immune System
Immune Systems
Major Histocompatibility Complex
B Cells
Amino Acids
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l. Atlan, H.,, and I. R. Cohen. 1998. Immune information, self-organization and meaning. Int. Immunol. 10:711717.
2. Ausubel, L. J.,, C. K. Kwan,., A. Sette,, V. Kuchroo,, and D. A. Hafler. 1996. Complementary mutations in an antigenic peptide allow for crossreactivity of autoreactive T-cell clones. Proc. Natl. Acad. Sci. USA 93:1531715322.
3. Baum, H.,, H. Davis,, and M. Peakman. 1996. Molecular mimicry in the MHC: hidden clues to autoimmunity? Immunol. Today 17:6470.
4. Ben-Nun, A.,, and I. R. Cohen. 1982. Spontaneous remission and acquired resistance to autoimmune encephalomyelitis (EAE) are associated with suppression of T cell reactivity: suppressed EAE effector T cells recovered as T cell lines. J. Immunol. 128:14501457.
5. Ben-Nun, A.,, H. Wekerle,, and I. R. Cohen. 1981. The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis. Eur. J. Immunol. 11:195199.
6. Bhardwaj, V.,, V. Kumar,, H. M. Geysen,, and E. E. Sercarz. 1993. Degenerate recognition of a dissimilar antigenic peptide by myelin basic protein-reactive T cells. Implications for thymic education and autoimmunity. J. Immunol. 151:50005010.
7. Birk, O. S.,, S. L. Gur,, D. Elias,, R. Margalit,, F. Mor,, P. Carmi,, J. Bockova,, D. M. Altmann,, and I. R. Cohen. 1999. The 60-kDa heat shock protein modulates allograft rejection. Proc. Natl. Acad. Sci. USA 96:51595163.
8. Bowman, M. A.,, E. H. Leiter,., and M. A. Atkinson. 1994. Prevention of diabetes in the NOD mouse: implications for therapeutic intervention in human disease. Immunol. Today 15:115120.
9. Burnet, F. M. 1959. The Clonal Selection Theory of Acquired Immunity. Cambridge University Press, Cambridge, United Kingdom.
10. Burnet, F. M. 1969. Self and Not-Self. Cambridge University Press, Cambridge, United Kingdom.
11. Cohen, I. R. 1992. The cognitive principle challenges clonal selection. Immunol. Today 13:441444.
12. Cohen, I. R. 1992. The cognitive paradigm and the immunological homunculus. Immunol. Today 13:490494.
13. Cohen, I. R. 1995. Language, meaning and the immune system. Isr. J. Med. Sci. 31:3637.
14. Cohen, I. R. 2000. Tending Adam's Garden: Evolving the Cognitive Immune Self. Academic Press, London, United Kingdom.
15. Cohen, I. R.,, and D. B. Young. 1991. Autoimmunity, microbial immunity and the immunological homunculus. Immunol. Today 12:105110.
16. Damian, R. T. 1964. Molecular mimicry: antigen sharing by parasite and host and its consequences. Am. Nat. 98:129149.
17. Damian, R. T. 1997. Parasite immune evasion and exploitation: reflections and projections. Parasitology 115:S169S175.
18. Fesel, C.,, and A. Coutinho. 1998. Dynamics of serum IgM autoreactive repertoires following immunization: strain specificity, inheritance and association with autoimmune disease susceptibility. Eur. J. Immunol. 28:36163629.
19. Fischer, H. P.,, C. E. Sharrock,, and G. S. Panayi. 1992. High frequency of cord blood lymphocytes against mycobacterial 65-kDa heat-shock protein. Eur. J. Immunol. 22:16671669.
20. Grencis, R. K.,, and G. M. Entwistle. 1997. Production of an interferon-gamma homologue by an intestinal nematode: functionally significant or interesting artifact? Parasitology 115:S101S106.
21. Haury, M.,, A. Sundblad,, A. Grandien,, C. Barreau,, A. Coutinho,, and A. Nobrega. 1997. The repertoire of serum IgM in normal mice is largely independent of external antigenic contact. Eur. J. Immunol. 27:15571563.
22. Hoffmann, J. A.,, F. C. Kafatos,, C. A. Janeway,, and R. A. Ezekowitz. 1999. Phylogenetic perspectives in innate immunity. Science 284:13131318.
23. Holoshitz, J.,, Y. Naparstek,, A. Ben-Nun,, and I. R. Cohen. 1983. Lines of T lymphocytes induce or vaccinate against autoimmune arthritis. Science 219:5658.
24. Klotz, I. M.,, and D. L. Hunston. 1975. Protein interactions with small molecules. Relationships between stoichiometric binding constants, site binding constants, and empirical binding parameters. J. Biol. Chem. 250:30013009.
25. Konen-Waizmann, S.,, A. Cohen,, M. Fridkin,, and I. R. Cohen. 1999. Self heat-shock protein (hsp60) peptide serves in a conjugate vaccine against a lethal pneumococcal infection. J. Infect. Dis. 179:403413.
26. Lacroix-Desmazes, S.,, S. V. Kaveri,, L. Mouthon,, A. Ayouba,, E. Malanchere,, A. Coutinho,, and M. D. Kazatchkine. 1998. Self-reactive antibodies (natural autoantibodies) in healthy individuals. J. Immunol. Methods 216:117137.
27. Lancet, D.,, E. Sadovsky,, and E. Seidemann. 1993. Probability model for molecular recognition in biological receptor repertoires: significance to the olfactory system. Proc. Natl. Acad. Sci. USA 90:37153719.
28. Mason, D. 1998. A very high level of crossreactivity is an essential feature of the T-cell receptor. Immunol. Today 19:395104.
29. McLaurin, J. A.,, D. Hafler,, and J. P. Antel. 1995. Reactivity of normal T-cell lines to MBP isolated from normal and multiple sclerosis white matter. J. Neurol. Sci. 128:205211.
30. Moalem, G.,, R. Leibowitz-Amit,, E. Yoels,, F. Mor,, I. R. Cohen,, and M. Schwartz. 1999. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat. Med. 5:4955.
31. 30a Mor, F.,, M. Kantorowitz,, and I. R. Cohen. Selection of anti-MBP T-cell lines in the Lewis rat: V-beta 8.2 dominance and CDR-3 motifs are dependent on serine at position 78 of MBP. J. Neuroimmunol., in press.
31. Nanda, N. K.,, K. K. Arzoo,, H. M. Geysen,, and E. E. Sercarz. 1995. Recognition of multiple peptide cores by a single T cell receptor. J. Exp. Med. 182:531539.
32. Oldstone, M. B. A. 1998. Molecular mimicry and immune-mediated diseases. FASEB J. 12:12551265.
33. Reizis, B.,, F. Mor,, M. Eisenstein,, H. Schild,, S. Stefanoviic,, H. G. Rammensee,, and I. R. Cohen. 1996. The peptide binding specificity of the MHC class III-A molecule of the Lewis rat, RT1.BI. Int. Immunol. 8:18251832.
34. Robey, E.,, and B. J. Fowlkes. 1994. Selective events in T cell development. Annu. Rev. Immunol. 12:675705.
35. Rook, G. A.,, and J. L. Stanford. 1998. Give us this day our daily germs. Immunol. Today 19:113116.
36. Rowley, D.,, and C. R. Jenkin. 1962. Antigenic cross-reaction between host and parasite as a possible cause of pathogenicity. Nature 193:151154.
37. Segel, L. A.,, R. L. Bar-Or. 1999. On the role of feedback in promoting conflicting goals of the adaptive immune system. J. Immunol. 163:13421349.
38. Schwartz, M.,, G. Moalem,, R. Leibowitz-Amit,, and I. R. Cohen. 1999. Innate and adaptive responses can be beneficial for CNS repair. Trends Neurosci. 22:295299.
39. Stollerman, G. H. 1998. The changing face of rheumatic fever in the 20th century. J. Med. Microbiol. 47:655657.
40. van Eden, W.,, J. Holoshitz,, Z. Nevo,, A. Frenkel,, A. Klajman,, I. R. Cohen. 1985. Arthritis induced by a T-lymphocyte clone that responds to Mycobacterium tuberculosis and to cartilage proteoglycans. Proc. Natl. Acad. Sci. USA 82:51175120.
41. van Eden, W.,, J. E. Thole,, R. van der Zee,, A. Noordzij,, J. D. van Embden,, E. J. Hensen,, and I. R. Cohen. 1988. Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis. Nature 331:171173.
42. Von Boehmer, H. 1990. Developmental biology of T cells in T cell-receptor transgenic mice. Annu. Rev. Immunol. 8:531556.
43. von Herrath, M. G.,, S. Guerder,, H. Lewicki,, R. A. Flavell,, and M. B. Oldstone. 1995. Coexpression of B7-1 and viral (“self”) transgenes in pancreatic beta cells can break peripheral ignorance and lead to spontaneous autoimmune diabetes. Immunity 3:727738.
44. von Herrath, M. G.,, C. F. Evans,, M. S. Horwitz,, and M. B. Oldstone. 1996. Using transgenic mouse models to dissect the pathogenesis of virus-induced autoimmune disorders of the islets of Langerhans and the central nervous system. Immunol. Rev. 152:111143.
45. Wekerle, H.,, M. Bradl,, C. Linington,, G. Kaab,, and K. Kojima. 1996. The shaping of the brain-specific T lymphocyte repertoire in the thymus. Immunol. Rev. 149:231243.

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