Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Anti-Acetylcholine Receptor CD4+ T Cells in Myasthenia Gravis: Epitope repertoire and T cell receptor gene usage

  • Chapter
Myasthenia Gravis

  • 241 Accesses

Abstract

Although the symptoms of myasthenia gravis (MG) are due to the binding of auto-antibodies to the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction (reviewed in [1]), the anti-AChR CD4+T cells have been intensely investigated, because they may be the prime movers in the pathogenesis of MG. Furthermore, specific immunosuppressive treatments targeted on the autoimmune CD4+ cells have proven successful in experimental autoimmune diseases, including the experimental model of MG, mouse experimental autoimmune MG (EAMG) ([2–4] and references therein).

Previously known as Bianca M. Conti-Tronconi

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Conti-Fine, B.M., M. Bellone, J.F. Howard Jr. and M.P. Protti. 1997. Myasthenia Gravis. The Immunobiology of an Autoimmune Disease. Neuroscience Intelligence Unit. R.G. Landes. Austin, TX, USA 1–230.

    Google Scholar 

  2. Karachunski, P.I., N. Ostlie. D. Okita, and B.M. Conti-Fine. 1997. Protection from experimental myasthenia gravis in C57B1/6 mice by sniffing of synthetic CD4+ T cells epitopes. J. Clin. Invest. 100: 3027.

    Article  PubMed  CAS  Google Scholar 

  3. Wu, B., C. Deng, E. Goluszko and P. Christadoss. 1997. Tolerance to a dominant T cell epitope in the acetylcholine receptor molecule induces epitope spread and suppresses murine myasthenia gravis. J. Immunol. 159: 3016.

    PubMed  CAS  Google Scholar 

  4. Karachunski, P.I., N.S. Ostlie, D. Okita, R. Garman and B.M. Conti-Fine. 1999. Subcutaneous administration of T epitope sequences of the acetylcholine receptor prevents experimental myasthenia gravis. J. Neuroimmunol. 93: 108.

    Article  PubMed  CAS  Google Scholar 

  5. Wang, Z.-Y, P.I. Karachunski, J.F. Howard Jr. and B.M. Conti-Fine. 1999. Myasthenia in SCID mice grafted with myasthenic patient lymphocytes. Role of CD4+ and CD8+ cells. Neurology 52: 484.

    Article  PubMed  CAS  Google Scholar 

  6. Conti-Tronconi, B.M., K.E. McLane, M.A. Raftery, S. Grando and M. P. Protti. 1994. The nicotinic acetylcholine receptor: Structure and autoimmune pathology. Cri. Rev. Biochem. Mol. Biol. 29: 69.

    Article  CAS  Google Scholar 

  7. Horton, R.H., A.A. Manfredi and B.M. Conti-Tronconi. 1993. The “embryonic” γ subunit of the nicotinic acetylcholine receptor is expressed in adult extrinsic ocular muscles. Neurology 43: 983.

    Article  PubMed  CAS  Google Scholar 

  8. Kaminski, HJ., L.L. Kushner and C.H. Block. 1996. Expression of acetylcholine receptor isoforms at extraocular muscle endplates. Invest. Opthalmol. Vis. Sci. 37: 345.

    CAS  Google Scholar 

  9. Hohlfeld, R. and H. Wekerle. 1994. The thymus in Myasthenia Gravis. Neurol. Clin. North America 12: 331.

    CAS  Google Scholar 

  10. Nelson, S. and B.M. Conti-Tronconi. 1990. Adult thymus expresses an embryonic muscle acetycholine receptor-like protein. J. Neuroimmunol. 29: 81.

    Article  PubMed  CAS  Google Scholar 

  11. Geuder, K.I., A. Marx, V. Witzemann, B. Schalke, K. Toyka, T. Kirchner, and H.K. Muller-Hermelink. 1992. Pathogenetic significance of fetal-type acetylcholine receptors on thymid myoid cells in myasthenia gravis. Dev. Immunol. 2: 69.

    Article  PubMed  CAS  Google Scholar 

  12. Kaminski, H.J., R.A. Fenstermaker, F.W. Abdul-Karim, J. Clayman, and R.L. Ruff. 1993. Acetylcholine receptor subunit gene expression in thymic tissue. Muscle Nerve 16: 1332.

    Article  PubMed  CAS  Google Scholar 

  13. Lindstrom, J., B. Einarson and J. Merlie. 1978. Immunization of rats with polypeptide chains from Torpedo acetylcholine receptor causes an autoimmune response to receptors in rat muscle. Proc. Natl. Acad. Sci. U.S.A. 75: 769.

    Article  PubMed  CAS  Google Scholar 

  14. Bellone, M., N. Ostlie, P.I. Karachunski and B.M. Conti-Tronconi. 1993. Cryptic epitopes on nicotinic acetylcholine receptor are recognized by autoreactive CD4+cells. J. Immunol. 151: 1025.

    PubMed  CAS  Google Scholar 

  15. Fujii, Y. and J. Lindstrom. 1988. Specificity of the T cell immune response to acetylcholine receptor in experimental autoimmune myasthenia gravis. Response to subunits and synthetic peptides. J. Immunol. 140: 1830.

    PubMed  CAS  Google Scholar 

  16. Raju, R., B. Diethelm-Okita, D. Okita and B.M. Conti-Fine. 1996. Epitopes repertoire of human CD4+ T lines propagated with tetanus toxoid or with synthetic tetanus toxoid sequences. J. Autoimmun. 9: 79.

    Article  PubMed  CAS  Google Scholar 

  17. Wang, Z.-Y., D. Okita, J.F. Howard Jr. and B.M. Conti-Fine. 1998. T cell recognition of the muscle acetylcholine receptor subunits in generalized and ocular myasthenia gravis. Neurology 50: 1045.

    Article  PubMed  CAS  Google Scholar 

  18. Wang, Z.-Y, B. Diethelm-Okita, D. Okita, J.H. Kaminski, J.F. Howard [jrJr. and B.M. Conti-Fine. Unstable T cell recognition of the human acetylcholine receptors in ocular myasthenia gravis. In preparation.

    Google Scholar 

  19. Stern, L.J., J.H. Brown, T.S. Jardetzky, J.C. Gorga, R.G. Urban, J.L. Strominger and D.C. Wiley. 1994. Crystal structure of the human class II MHC protein HLADRl complexed with an influenza virus peptide. Nature 368: 215.

    Article  PubMed  CAS  Google Scholar 

  20. Marx, A., A. Willisch, V. Hoffacker, A. Schultz, S. Tzaetos and H.K. Muller-Hermelink. 1999. Lack of acetylcholine receptor delta subunit message and protein in human thymuses suggests the occurence of ‘triplet receptors’ in the thymic myoid cells. This book.

    Google Scholar 

  21. Miller, S.D., B.L. McRae, C.L. Vanderlugt, K.M. Nikcevich, J.G. Pope, L. Pope and W.J. Karpus. 1995. Evolution of the T-cell repertoire during the course of experimental immune-mediated demyelinating diseases. Immunol. Rev. 144: 225.

    Article  PubMed  CAS  Google Scholar 

  22. Bellone, M., N. Ostlie, P.I. Karachunski and B.M. Conti-Tronconi. 1993. Cryptic epitopes on nicotinic acetylcholine receptor are recognized by autoreactive CD4+cells. J. Immunol. 151: 1025.

    PubMed  CAS  Google Scholar 

  23. Shenoy, M., E. Goluszko and P. Christadoss. 1994. The pathogenic role of acetylcholine receptor α chain epitope within αl46-162 in the development of experimental autoimmune myasthenia gravis in C57BL6 mice. Clin. Immunol. Immunopathol. 73: 338.

    Article  PubMed  CAS  Google Scholar 

  24. Conti-Fine B.M., D. Navaneetham, P.I. Karachunski, R. Raju, B. Diethelm-okita, D.K. Okita, J.F. Howard Jr. and Z.-Y. Wang. 1998. T-cell recognition of the acetylcholine receptor in myasthenia gravis. Ann. N.Y. Acad. Sci. 841: 283.

    Article  PubMed  CAS  Google Scholar 

  25. Manfredi, A.A., M.P. Protti, X.D. Wu, J.F. Howard Jr. and B.M. Conti-Tronconi. 1992. CD4+T-epitope repertoire on the human acetylcholine receptor α subunit in severe myasthenia gravis. A study with synthetic peptides. Neurology 42: 1092.

    Article  PubMed  CAS  Google Scholar 

  26. Manfredi, A.A., M.P. Protti, M.W.M. Dalton, J.F. Howard Jr. and B.M. Conti-Tronconi. 1993. T helper cell recognition of muscle acetylcholine receptor in myasthenia gravis: epitopes on the γ and δ subunits. J. Clin. Invest. 92: 1055.

    Article  PubMed  CAS  Google Scholar 

  27. Wang, Z.-Y., D. Okita, J.F. Howard Jr. and B.M. Conti-Fine. 1998. CD4+ T cell recognition of the ε subunit of human muscle acetylcholine receptor in myasthenia gravis. J. Neuroimmunol, 91: 33.

    Article  PubMed  CAS  Google Scholar 

  28. Oda, K. and Y. Ito. 1981. Myasthenia gravis: antibodies to acetylcholine receptor in ocular myasthenia gravis. J. Neurol. 225: 251.

    Article  PubMed  CAS  Google Scholar 

  29. Kaminski, H.J., L.L. Kusner, K.V. Nash, and R.L. Ruff. 1995. The γ-subunit of the acetylcholine receptor is not expressed in the levator palpebrae superioris. Neurology 45: 516.

    Article  PubMed  CAS  Google Scholar 

  30. MacLennon, C, D. Beeson, A.-M. Buijs, A. Vincent and J. Newsom-Davis. 1997. Acetylcholine receptor expression in the human extraocular muscles and their susceptability to myasthenia gravis. Annal. Neurol. 41: 423.

    Article  Google Scholar 

  31. Protti, M.P., A.A. Manfredi, C. Straub, J.F. Howard Jr. and B.M. Conti-Tronconi. 1990. Immunodominant regions for T helper sensitization on the human nicotinic receptor subunit in myasthenia gravis. Proc. Natl. Acad. Sci. U.S.A. 87: 7792.

    Article  PubMed  CAS  Google Scholar 

  32. Moiola, L., P. Karachunski, M.P. Protti, J.F. Howard Jr. and B.M. Conti-Tronconi. 1994. Epitopes on the subunit of human muscle acetylcholine receptor recognized by CD4+ cells of myasthenia gravis patients and healthy subjects. J. Clin. Invest. 93: 1020.

    Article  PubMed  CAS  Google Scholar 

  33. Protti, M.P, A.A. Manfredi, X.D. Wu, L. Moiola, J.F. Howard Jr. and B.M. Conti-Tronconi. 1991. Myasthenia Gravis: T epitopes of the δ subunit of human muscle acetylcholine receptor. J. Immunol. 146: 2253.

    PubMed  CAS  Google Scholar 

  34. Protti, M.P., A.A. Manfredi, X.D. Wu, L. Moiola, M.W.M. Dalton, J.F. Howard Jr., and B.M. Conti-Tronconi. 1992. Myasthenia Gravis. CD4+T epitopes on the embryonic γ subunit of human muscle acetylcholine receptor. J. Clin. Invest. 90: 1558.

    Article  PubMed  CAS  Google Scholar 

  35. Wang, Z.-Y., D.K. Okita, J.F. Howard Jr, and B.M. Conti-Fine. 1997. Th1 epitope repertoire on the α subunit of human muscle acetylcholine receptor in myasthenia gravis. Neurology 48: 1643.

    Article  PubMed  CAS  Google Scholar 

  36. Conti-Fine, B.M., K.E. McLane and S. Lei. 1996. Antibodies as tools to study the structure of membrane proteins, the case of the nicotinic acetylcholine receptor. Ann. Rev. Biophys. Biomol. Struc. 25: 197.

    Article  CAS  Google Scholar 

  37. Raju, R., D. Navaneetham, D.K. Okita, B. Diethelm-Okita, D. McCormick, and B.M. Conti-Fine. 1995. Epitopes for human CD4+ T cells on diphtheria toxin: structural features of sequence segments forming epitopes recognized by most subjects. Eur. J. Immunol. 25: 3207.

    Article  PubMed  CAS  Google Scholar 

  38. Navarrete, C. and G.F. Bottazzo. 1993. In search of TCR restriction in autoreactive T cell in human autoimmunity: why is it so elusive? Clin. Exp. Immunol. 91: 189.

    Article  CAS  Google Scholar 

  39. Casanova, J. and J.L. Maryanski. 1993. Antigen-selected T-cell receptor diversity and self-nonself homology. Immunol. Today 14: 391.

    Article  PubMed  CAS  Google Scholar 

  40. Moiola, L., M.P. Protti, J.F. Howard and B.M. Conti-Tronconi. 1994. Myasthenia Gravis: Residues of the α and γ subunits of muscle acetylcholine receptor involved in formation of immunodominant CD4+ epitopes. J. Immunol. 152: 4686.

    PubMed  CAS  Google Scholar 

  41. Raju, R., D. Navaneetham, M.P. Protti, R.M. Horton, B.L. Hoppe, J. F. Howard Jr. and B.M. Conti-Fine. 1997. Preferential TCR Vβ usage by acetylcholine receptor specific CD4+ T cells in myasthenia gravis. J. Autoimmun. 10: 203.

    Article  PubMed  CAS  Google Scholar 

  42. Melms, A., J.R. Oksenberg, G. Malcherek, R. Schoepfer, C.A. Müller, J. Lindstrom and L. Steinman. 1993. T cell receptor gene usage of acetylcholine receptor-specific T-helper cells. Ann. N.Y.Acad. Sci. 681: 313.

    Article  PubMed  CAS  Google Scholar 

  43. Grunewald, J., R. Ahlberg, A.-K. Lefvert, H. Dersimonian, H. Wigzell and C. H. Janson. 1991. Abnormal T-cell expansion and V-gene usage in myasthenia gravis patients. Scand. J. Immunol. 34: 161.

    Article  PubMed  CAS  Google Scholar 

  44. Meinl, E., F. Weber, K. Drexler, G. Morelle, M. Ott, G. Saruhan-Direskeneli, N. Goebels, B. Ertl, G. Jechart, G. Giegerich, S. Schonbeck, N. Bannwarth, H. Wekerle and R. Hohlfeld. 1993. Myelin basic protein-specific T lymphocyte repertoire in multiple sclerosis. Complexity of the response and dominance of nested epitopes due to recruitment of multiple T cell clones. J. Clin. Invest. 92: 2633.

    Article  PubMed  CAS  Google Scholar 

  45. Vanderlugt, C.J. and S.D. Miller. 1996. Epitope spreading. Current Opin. Immunol. 8:831.

    Article  CAS  Google Scholar 

  46. Lider, O., A. Miller, S. Miron, R. Hershkoviz, H.L. Weiner, X. Zhang and E. Heber-Katz. 1991. Nonencephalitogenic CD4-CD8- Vα2Vβ8.2+ anti-myelin basic protein rat T lymphocytes inhibit disease induction. J. Immunol. 147: 1208.

    PubMed  CAS  Google Scholar 

  47. Woodland, D.L. and M.A. Blackman. 1992. Retroviral Super-Antigens and T cells. Intl. Rev. Immunol. 8: 311.

    Article  CAS  Google Scholar 

  48. Schoenbeck S., F. Padberg, R. Hohlfeld and H. Wekerle. 1992. Transplantation of thymic autoimmune microenvironment to severe combined immunodeficiency mice. A new model of myasthenia gravis. J. Clin. Invest. 90: 245.

    Article  Google Scholar 

  49. Meinl, E., W.E.F. Klinkert and H. Wekerle. 1991. The thymus in myasthenia gravis: Changes typical for the human disease are absent in experimental autoimmune myasthenia gravis of the Lewis rat. Am. J. Pathol. 139: 995.

    PubMed  CAS  Google Scholar 

  50. Navaneetham, D., A.S. Penn, J.F. Howard Jr. and B.M. Conti-Fine. 1998. TCR-Vβ usage in the thymus and blood of myasthenia gravis patients. J. Autoimmun. [vn11:621.

    Google Scholar 

  51. Tesch, H., R. Hohlfeld and K.V. Toyka. 1989. Analysis of immunoglobulin and T cell receptor gene rearrangements in the thymus of myasthenia gravis patients. J. Neuroimmunol. 21: 169.

    Article  PubMed  CAS  Google Scholar 

  52. Truffault, F., S. Cohen-Kaminsky, I. Khalil, P. Levasseur and S. Berrih-Aknin. 1997. Altered intrathymic T-cell repertoire in human myathenia gravis. Ann. Neurol. 41: 731.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, St. Paul, MN, 55108, USA

    Bianca M. Conti-Fine, Zeng-Yu Wang, Raghavanpillai Raju & Duraiswamy Navaneetham

  2. Department of Pharmacology, School of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA

    Bianca M. Conti-Fine & Duraiswamy Navaneetham

  3. Department of Neurology, University of North Carolina at Chapel Hill, NC, 27599, USA

    James F. Howard Jr.

  4. Department of Immunology, Mayo Clinic, Rochester, MN, 55905, USA

    James F. Howard Jr.

Authors
  1. Bianca M. Conti-Fine
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zeng-Yu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raghavanpillai Raju
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. James F. Howard Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Duraiswamy Navaneetham
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA

    Premkumar Christadoss (Professor) (Professor)

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Conti-Fine, B.M., Wang, ZY., Raju, R., Howard, J.F., Navaneetham, D. (2000). Anti-Acetylcholine Receptor CD4+ T Cells in Myasthenia Gravis: Epitope repertoire and T cell receptor gene usage. In: Christadoss, P. (eds) Myasthenia Gravis. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-4060-7_8

Download citation

  • DOI: https://doi.org/10.1007/978-94-011-4060-7_8

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-5787-5

  • Online ISBN: 978-94-011-4060-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation