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A peptide vaccine that prevents experimental autoimmune myasthenia gravis by specifically blocking T cell help
Author(s) -
ARAGA SHIGERU,
XU LIKANG,
NAKASHIMA KENJI,
VILLAIN MATTEO,
BLALOCK J. EDWIN
Publication year - 2000
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.14.1.185
Subject(s) - myasthenia gravis , epitope , acetylcholine receptor , monoclonal antibody , t cell , autoantibody , immunology , autoimmune disease , polyclonal antibodies , receptor , monoclonal , microbiology and biotechnology , chemistry , antigen , biology , antibody , immune system , biochemistry
Myasthenia gravis (MG) and its animal model, experimental autoimmune (EA) MG, are caused by T cell‐dependent autoantibodies that react with the nicotinic acetylcholine receptor (AChR) on muscle and interfere with neuromuscular transmission. Thus, selective inactivation of CD4 + AChR‐specific T helper cells should lower AChR Ab levels and ameliorate disease. In the Lewis rat model of EAMG, a chain residues 100–116 of the AChR represent the dominant T cell epitope, which is important in helping Ab responses to this autoantigen. In the present report, we have applied a new design technique that requires no knowledge of Ag receptor sequences on errant T cells in order to develop a synthetic peptide vaccine against T cells reactive with the aforementioned T cell epitope. Immunization with the peptide 1) induced polyclonal and monoclonal Ab, which inhibited AChR 100–116 stimulation of AChR‐sensitized lymphocytes and recognized Vβ15 containing T cell receptors on AChR 100–116‐specific T cell lines and clones; 2) lowered AChR Ab levels; 3) reduced the loss of muscle AChR; and 4) lessened the incidence and severity of EAMG. These findings suggest a new strategy for the functional abrogation of epitope‐specific T cells that could have potential application to human autoimmune diseases.—Araga, S., Xu, L., Nakashima, K., Villain, M., Blalock, J. E. A peptide vaccine that prevents experimental autoimmune myasthenia gravis by specifically blocking T cell help. FASEB J. 14, 185–196(2000)