Abstract |
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, alpha 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 Vbeta15 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.
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Authors | S Araga, L Xu, K Nakashima, M Villain, J E Blalock |
Journal | FASEB journal : official publication of the Federation of American Societies for Experimental Biology
(FASEB J)
Vol. 14
Issue 1
Pg. 185-96
(Jan 2000)
ISSN: 0892-6638 [Print] United States |
PMID | 10627293
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Peptides
- Receptors, Antigen, T-Cell
- Receptors, Cholinergic
- Vaccines
- DNA
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Topics |
- Amino Acid Sequence
- Animals
- Base Sequence
- DNA
- Female
- Humans
- Molecular Sequence Data
- Myasthenia Gravis
(prevention & control)
- Peptides
(immunology)
- Rats
- Rats, Inbred Lew
- Receptors, Antigen, T-Cell
(chemistry, immunology)
- Receptors, Cholinergic
(chemistry, immunology)
- T-Lymphocytes
(immunology)
- Vaccines
(immunology)
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