• 1
    Lindstrom, J. M., Seybold, M. E., Lennon, V. A., Whittingham, S. and Duane, D. D., Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology 1976. 26: 10541059.
  • 2
    Toyka, K. V., Drachman, D. B., Griffin, D. E., Pestronk, A., Winkelstein, J. A., Fishbeck, K. H. and Kao, I., Myasthenia gravis. Study of humoral immune mechanisms by passive transfer to mice. N. Engl. J. Med. 1977. 296: 125131.
  • 3
    Newsom-Davis, J., Vincent, A., Wilson, S. G., Ward, C. D., Pinching, A. J. and Hawkey, C., Plasmapheresis for myasthenia gravis. N. Engl. J. Med. 1978. 298: 456457.
  • 4
    Hoch, W., McConville, J., Helms, S., Newsom-Davis, J., Melms, A. and Vincent, A., Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat. Med. 2001. 7: 365368.
  • 5
    Vincent, A. and Drachman, D. B., Myasthenia gravis. Adv. Neurol. 2002. 88: 159188.
  • 6
    Hohlfeld, R., Toyka, K. V., Heininger, K., Grosse-Wilde, H. and Kalies, I., Autoimmune human T lymphocytes specific for acetylcholine receptor. Nature 1984. 310: 244246.
  • 7
    Lennon, V. A., Lindstrom, J. M. and Seybold, M. E., Experimental autoimmune myasthenia gravis: Cellular and humoral immune responses. Ann. N. Y. Acad. Sci. 1976. 274: 283299.
  • 8
    Fujii, Y. and Lindstrom, J., Regulation of antibody production by helper T cell clones in experimental autoimmune myasthenia gravis. J. Immunol. 1988. 141: 33613369.
  • 9
    Sommer, N., Willcox, N., Harcourt, G. C. and Newsom-Davis, J., Myasthenic thymus and thymoma are selectively enriched in acetylcholine receptor-reactive T cells. Ann. Neurol. 1990. 28: 312319.
  • 10
    Truffault, F., Cohen-Kaminsky, S., Khalil, I., Levasseur, P. and Berrih-Aknin, S., Altered intrathymic T-cell repertoire in human myasthenia gravis. Ann. Neurol. 1997. 41: 731741.
  • 11
    Nenninger, R., Schultz, A., Hoffacker, V., Helmreich, M., Wilisch, A., Vandekerckhove, B., Hunig, T. et al., Abnormal thymocyte development and generation of autoreactive T cells in mixed and cortical thymomas. Lab. Invest. 1998. 78: 743753.
  • 12
    Elson, C. J. and Barker, R. N., Helper T cells in antibody-mediated, organ-specific autoimmunity. Curr. Opin. Immunol. 2000. 12: 664669.
  • 13
    Roxanis, I., Micklem, K., McConville, J., Newsom-Davis, J. and Willcox, N., Thymic myoid cells and germinal center formation in myasthenia gravis; possible roles in pathogenesis. J. Neuroimmunol. 2002. 125: 185197.
  • 14
    Vincent, A., Unravelling the pathogenesis of myasthenia gravis. Nat. Rev. Immunology 2002. 2: 797804.
  • 15
    Compston, D. A., Vincent, A., Newsom-Davis, J. and Batchelor, J. R., Clinical, pathological, HLA antigen and immunological evidence for disease heterogeneity in myasthenia gravis. Brain 1980. 103: 579601.
  • 16
    Aarli, J. A., Romi, F., Skeie, G. O. and Gilhus, N. E., Myasthenia gravis in individuals over 40. Ann. N. Y. Acad. Sci. 2003. 998: 424431.
  • 17
    Vincent, A., Clover, L., Buckley, C., Grimley Evans, J., Rothwell, P. M. and the UK Myasthenia Gravis Survey, Evidence of underdiagnosis of myasthenia gravis in older people. J. Neurol. Neurosurg. Psychiatry 2003. 74: 11051108.
  • 18
    Somnier, F. E., Increasing incidence of late-onset anti-AChR antibody-seropositive myasthenia gravis. Neurology 2005. 65: 928930.
  • 19
    Protti, M. P., Manfredi, A. A., Straub, C., Howard, J. F. Jr. and Conti-Tronconi, B. M., CD4+ T cell response to the human acetylcholine receptor alpha subunit in myasthenia gravis. A study with synthetic peptides. J. Immunol. 1990. 144: 12761281.
  • 20
    Berrih-Aknin, S., Cohen-Kaminsky, S., Lepage, V., Neumann, D., Bach, J. F. and Fuchs, S., T-cell antigenic sites involved in myasthenia gravis: Correlations with antibody titre and disease severity. J. Autoimmun. 1991. 4: 137153.
  • 21
    Ong, B., Willcox, N., Wordsworth, P., Beeson, D., Vincent, A., Altmann, D., Lanchbury, J. S. et al., Critical role for the Val/Gly86 HLA-DR beta dimorphism in autoantigen presentation to human T cells. Proc. Natl. Acad. Sci. USA 1991. 88: 73437347.
  • 22
    Sommer, N., Harcourt, G. C., Willcox, N., Beeson, D. and Newsom-Davis, J., Acetylcholine receptor-reactive T lymphocytes from healthy subjects and myasthenia gravis patients. Neurology 1991. 41: 12701276.
  • 23
    Salvetti, M., Jung, S., Chang, S. F., Will, H., Schalke, B. C. and Wekerle, H., Acetylcholine receptor-specific T-lymphocyte clones in the normal human immune repertoire: target epitopes, HLA restriction, and membrane phenotypes. Ann. Neurol. 1991. 29: 508516.
  • 24
    Harcourt, G. C., Sommer, N., Rothbard, J., Willcox, H. N. and Newsom-Davis, J., A juxta-membrane epitope on the human acetylcholine receptor recognized by T cells in myasthenia gravis. J. Clin. Invest. 1988. 82: 12951300.
  • 25
    Melms, A., Malcherek, G., Gern, U., Wiethölter, H., Müller, C. A., Schoepfer, R. and Lindstrom, J., T cells from normal and myasthenic individuals recognize the human acetylcholine receptor: Heterogeneity of antigenic sites on the alpha-subunit. Ann. Neurol. 1992. 31: 311318.
  • 26
    Link, H., Xu, Z. Y., Melms, A., Kalbacher, H., Sun, J. B., Wang, Z. Y., Fredrikson, S. and Olsson, T., The T-cell repertoire in myasthenia gravis involves multiple cholinergic receptor epitopes. Scand. J. Immunol. 1992. 36: 405414.
  • 27
    Moiola, L., Protti, M. P., McCormick, D., Howard, J. F. and Conti-Tronconi, B. M., Myasthenia gravis. Residues of the alpha and gamma subunits of muscle acetylcholine receptor involved in formation of immunodominant CD4+ epitopes. J. Immunol. 1994. 152: 46864698.
  • 28
    Hawke, S., Matsuo, H., Nicolle, M., Malcherek, G., Melms, A. and Willcox, N., Autoimmune T cells in myasthenia gravis: Heterogeneity and potential for specific immunotargeting. Immunol. Today 1996. 17: 307311.
  • 29
    Nagvekar, N., Corlett, L., Jacobson, L. W., Matsuo, H., Chalkley, R., Driscoll, P. C., Deshpande, S. et al., Scanning a DRB3*0101 (DR52a)-restricted epitope cross-presented by DR3: Overlapping and artificial determinants in the human acetylcholine receptor. J. Immunol. 1999. 162: 40794087.
  • 30
    Mygland, A., Vincent, A., Newsom-Davis, J., Kaminski, H., Zorzato, F., Agius, M., Gilhus, N. E. and Aarli, J. A., Autoantibodies in thymoma-associated myasthenia gravis with myositis or neuromyotonia. Arch. Neurol. 2000. 57: 527531.
  • 31
    Meager, A., Wadhwa, M., Dilger, P., Bird, C., Thorpe, R., Newsom-Davis, J. and Willcox, N., Anti-cytokine autoantibodies in autoimmunity: Preponderance of neutralising autoantibodies against interferon-alpha, interferon-omega and interleukin-12 in patients with thymoma and/or myasthenia gravis. Clin. Exp. Immunol. 2003. 132: 128136.
  • 32
    Xu, L., Villain, M., Galin, F. S., Araga, S. and Blalock, J. E., Specific immunotherapy of experimental myasthenia gravis in vitro: The “guided missile” strategy. Cell. Immunol. 2001. 208: 137147.
  • 33
    Gigliotti, D., Lefvert, A. K., Jeddi-Tehrani, M., Esin, S., Hodara, V., Pirskanen, R., Wigzell, H. and Andersson, R., Overexpression of select T cell receptor V beta gene families within CD4+ and CD8+ T cell subsets of myasthenia gravis patients: A role for superantigen(s)? Mol. Med. 1996. 2: 452459.
  • 34
    Navaneetham, D., Penn, A. S., Howard, J. F. Jr. and Conti-Fine, B. M., TCR-Vbeta usage in the thymus and blood of myasthenia gravis patients. J. Autoimmun. 1998. 11: 621633.
  • 35
    Xu, B. Y., Giscombe, R., Soderlund, A., Troye-Blomberg, M., Pirskanen, R. and Lefvert, A. K., Abnormal T cell receptor V gene usage in myasthenia gravis: Prevalence and characterization of expanded T cell populations. Clin. Exp. Immunol. 1998. 113: 456464.
  • 36
    Kolowos, W., Schmitt, M., Herrman, M., Harrer, E., Low, P., Kalden, J. R. and Harrer, T., Biased TCR repertoire in HIV-1-infected patients due to clonal expansion of HIV-1-reverse transcriptase-specific CTL clones. J. Immunol. 1999. 162: 75257533.
  • 37
    Epperson, D. E., Nakamura, R., Saunthararajah, Y., Melenhorst, J. and Barrett, A. J., Oligoclonal T cell expansion in myelodysplastic syndrome: Evidence for an autoimmune process. Leuk. Res. 2001. 25: 10751083.
  • 38
    Jacobsen, M., Cepok, S., Quak, E., Happel, M., Gaber, R., Ziegler, A., Schock, S. et al., Oligoclonal expansion of memory CD8+ T cells in cerebrospinal fluid from multiple sclerosis patients. Brain 2002. 125: 538550.
  • 39
    Matsumoto, Y., Matsuo, H., Sakuma, H., Park, I. K., Tsukada, Y., Kohyama, K., Kondo, T. et al., CDR3 spectratyping analysis of the TCR repertoire in myasthenia gravis. J. Immunol. 2006. 176: 51005107.
  • 40
    Posnett, D. N., Sinha, R., Kabak, S. and Russo, C., Clonal populations of T cells in normal elderly humans: The T cell equivalent to “benign monoclonal gammopathy”. J. Exp. Med. 1994. 179: 609618.
  • 41
    Schwab, R., Szabo, P., Manavalan, J. S., Weksler, M. E., Posnett, D. N., Pannetier, C., Kourilsky, P. and Even, J., Expanded CD4+ and CD8+ T cell clones in elderly humans. J. Immunol. 1997. 158: 44934499.
  • 42
    Haynes, B. F., Markert, M. L., Sempowski, G. D., Patel, D. D. and Hale, L. P., The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection. Annu. Rev. Immunol. 2000. 18: 529560.
  • 43
    Vinuesa, C. G., Tangye, S. G., Moser, B. and Mackay, C. R., Follicular B helper T cells in antibody responses and autoimmunity. Nat. Rev. Immunol. 2005. 5: 853865.
  • 44
    Pette, M., Fujita, K., Wilkinson, D., Altmann, D. M., Trowsdale, J., Giegerich, G., Hinkkanen, A. et al., Myelin autoreactivity in multiple sclerosis: Recognition of myelin basic protein in the context of HLA-DR2 products by T lymphocytes of multiple-sclerosis patients and healthy donors. Proc. Natl. Acad. Sci. USA 1990. 87: 79687972.
  • 45
    Day, C. L., Seth, N. P., Lucas, M., Appel, H., Gauthier, L., Lauer, G. M., Robbins, G. K. et al., Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers. J. Clin. Invest. 2003. 112: 831842.
  • 46
    Kotzin, B. L., Karuturi, S., Chou, Y. K., Lafferty, J., Forrester, J. M., Better, M., Nedwin, G. E. et al., Preferential T-cell receptor beta-chain variable gene use in myelin basic protein-reactive T-cell clones from patients with multiple sclerosis. Proc. Natl. Acad. Sci. USA 1991. 88: 91619165.
  • 47
    Wagner, U. G., Koetz, K., Weyand, C. M. and Goronzy, J. J., Perturbation of the T cell repertoire in rheumatoid arthritis. Proc. Natl. Acad. Sci. USA 1998. 95: 1444714452.
  • 48
    Goebels, N., Hofstetter, H., Schmidt, S., Brunner, C., Wekerle, H. and Hohlfeld, R., Repertoire dynamics of autoreactive T cells in multiple sclerosis patients and healthy subjects. Epitope spreading versus clonal persitence. Brain 2000. 123: 508518.
  • 49
    Koga, M., Yuki, N., Tsukada, Y., Hirata, K. and Matsumoto, Y., CDR3 spectratyping analysis of the T cell receptor repertoire in Guillain–Barre and Fisher syndromes. J. Neuroimmunol. 2003. 141: 112117.
  • 50
    Callan, M. F. and McMichael, A. J., T cell receptor usage in infectious disease. Semin. Immunopathol. 1999. 21: 3754.
  • 51
    Jambou, F., Zhang, W., Menestrier, M., Klingel-Schmitt, I., Michel, O., Caillat-Zucman, S., Aissaoui, A. et al., Circulating regulatory anti-T cell receptor antibodies in patients with myasthenia gravis. J. Clin. Invest. 2003. 112: 265274.
  • 52
    Hoffacker, V., Schultz, A., Tiesinga, J. J., Gold, R., Schalke, B., Nix, W., Kiefer, R. et al., Thymomas alter the T-cell subset composition in the blood: A potential mechanism for thymoma-associated autoimmune disease. Blood. 2000. 96: 38723879.
  • 53
    Buckley, C., Douek, D., Newsom-Davis, J., Vincent, A. and Willcox, N., Mature, long-lived CD4+ and CD8+ T cells are generated by the thymoma in myasthenia gravis. Ann. Neurol. 2001. 50: 6472.
  • 54
    Ströbel, P., Helmreich, M., Menioudakis, G., Lewin, S. R., Rudiger, T., Bauer, A., Hoffacker, V. et al., Paraneoplastic myasthenia gravis correlates with generation of mature naive CD4(+) T cells in thymomas. Blood 2002. 100: 159166.
  • 55
    Lang, B. and Willcox, N., Autoantibodies in neuromuscular autoimmune disorders. Expert. Rev. Clin. Immunol. 2006. 2: 293307.
  • 56
    Fletcher, J. M, Vukmanovic-Stejic, M., Dunne, P. J., Birch, K. E., Cook, J. E., Jackson, S. E., Salmon, M. et al., Cytomegalovirus-specific CD4+ T cells in healthy carriers are continuously driven to replicative exhaustion. J. Immunol. 2005. 175: 82188225.
  • 57
    Skeie, G. O., Bentsen, P. T., Freiburg, A., Aarli, J. A. and Gilhus, N. E., Cell-mediated immune response against titin in myasthenia gravis: Evidence for the involvement of Th1 and Th2 cells. Scand. J. Immunol. 1998. 47: 7681.
  • 58
    Balasa, B. and Sarvetnick, N., Is pathogenic humoral autoimmunity a Th1 response? Lessons from (for) myasthenia gravis. Immunol. Today 2000. 21: 1923.
  • 59
    Moulian, N., Bidault, J., Truffault, F., Yamamoto, A. M., Levasseur, P. and Berrih-Aknin, S., Thymocyte Fas expression is dysregulated in myasthenia gravis patients with anti-acetylcholine receptor antibody. Blood 1997. 89: 32873295.
  • 60
    Moiola, L., Galbiati, F., Martino, G., Amadio, S., Brambilla, E., Comi, G., Vincent, A. et al., IL-12 is involved in the induction of experimental autoimmune myasthenia gravis, an antibody-mediated disease. Eur. J. Immunol. 1998. 28: 24872497.
  • 61
    Nagvekar, N., Moody, A. M., Moss, P., Roxanis, I., Curnow, J., Beeson, D., Pantic, N. et al., A pathogenetic role for the thymoma in myasthenia gravis. Autosensitization of IL-4- producing T cell clones recognizing extracellular acetylcholine receptor epitopes presented by minority class II isotypes. J. Clin. Invest. 1998. 101: 22682277.
  • 62
    Hill, M., Beeson, D., Moss, P., Jacobson, L., Bond, A., Corlett, L., Newsom-Davis, J. et al., Early onset myasthenia gravis: A recurring T-cell epitope in the adult specific epsilon subunit presented by the susceptibility allele HLA-DR52a. Ann. Neurol. 1999. 45: 224231.
  • 63
    Johansson-Lindbom, B., Ingvarsson, S. and Borrebaeck, C. A., Germinal centers regulate human Th2 development. J. Immunol. 2003. 171: 16571666.
  • 64
    Kim, C. H., Rott, L. S., Clark-Lewis, I., Campbell, D. J., Wu, L. and Butcher, E. C., Subspecialization of CXCR5+ T cells: B helper activity is focused in a germinal center-localized subset of CXCR5+ T cells. J. Exp. Med. 2001. 193: 13731381.
  • 65
    Warnatz, K., Dissecting CXCR5+ T cell populations – on the quest for a better understanding of B cell help during T dependent antibody responses. Eur. J. Immunol. 2006. 36: 16621664.
  • 66
    Rasheed, A. U., Rahn, H. P., Sallusto, F., Lipp, M. and Muller, G., Follicular B helper T cell activity is confined to CXCR5(hi)ICOS(hi) CD4 T cells and is independent of CD57 expression. Eur. J. Immunol. 2006. 36: 18921903.
  • 67
    Hemmer, B., Gran, B., Zhao, Y., Marques, A., Pascal, J., Tzou, A., Kondo, T. et al., Identification of candidate T-cell epitopes and molecular mimics in chronic Lyme disease. Nat. Med. 1999. 5: 13751382.
  • 68
    Dornmair, K., Goebels, N., Weltzien, H. U., Wekerle, H. and Hohlfeld, R., T-cell-mediated autoimmunity: Novel techniques to characterize autoreactive T-cell receptors. Am. J. Pathol. 2003. 163: 12151226.
  • 69
    Tzartos, S. J., Barkas, T., Cung, M. T., Mamalaki, A., Marraud, M., Orlewski, P., Papanastasiou, D. et al., Anatomy of the antigenic structure of a large membrane autoantigen, the muscle-type nicotinic acetylcholine receptor. Immunol. Rev. 1998. 163: 89120.
  • 70
    Vincent, A., Willcox, N., Hill, M., Curnow, J., MacLennan, C. and Beeson, D., Determinant spreading and immune responses to acetylcholine receptors in myasthenia gravis. Immunol. Rev. 1998. 164: 157168.
  • 71
    Besinger, U. A., Toyka, K. V., Hömberg, M., Heininger, K., Hohlfeld, R. and Fateh-Moghadam, A., Myasthenia gravis: Long-term correlation of binding and bungarotoxin blocking antibodies against acetylcholine receptors with changes in disease severity. Neurology 1983. 33: 13161321.
  • 72
    Muraro, P. A., Jacobsen, M., Necker, A., Nagle, J. W., Gaber, R., Sommer, N., Oertel, W. H. et al., Rapid identification of local T cell expansion in inflammatory organ diseases by flow cytometric T cell receptor Vbeta analysis. J. Immunol. Methods 2000. 246: 131143.
  • 73
    Genevée, C., Diu, A., Nierat, J., Caignard, A., Dietrich, P. Y., Ferradini, L., Roman-Roman, S. et al., An experimentally validated panel of subfamily-specific oligonucleotide primers (Vα1-w24/Vβ1-w24) for the study of human T cell receptor variable V gene segment usage by polymerase chain reaction. Eur. J. Immunol. 1992. 22: 12611269.
  • 74
    Schreuder, G. M., Hurley, C. K., Marsh, S. G., Lau, M., Fernandez-Vina, M., Noreen, H. J., Setterholm, M. and Maiers, M., The HLA Dictionary 2004: A summary of HLA-A, -B, -C, -DRB1/3/4/5 and -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens. Int. J. Immunogenet. 2005. 32: 1969.