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A peptide vaccine that prevents experimental autoimmune myasthenia gravis by specifically blocking T cell help

SHIGERU ARAGA^*,, LIKANG XU^*, KENJI NAKASHIMA, MATTEO VILLAIN^* and J. EDWIN BLALOCK^*1

^* Department of Physiology and Biophysics and the Center for Neuroimmunology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA; and
Division of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yanago City 683, Japan

¹Correspondence: University of Alabama at Birmingham, Department of Physiology and Biophysics, 1918 University Blvd., MCLM 896, Birmingham, AL 35294-0005, USA. E-mail: Blalock{at}uab.edu

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, 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 Vß15 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.

Key Words: complementary peptide • T cell receptor • anti-clonotypic antibody • autoimmunity • acetylcholine receptor

This article has been cited by other articles:

				J. L. McAnally, L. Xu, M. Villain, and J. E. Blalock The Role of Adjuvants in the Efficacy of a Peptide Vaccine for Myasthenia Gravis Experimental Biology and Medicine, April 1, 2001; 226(4): 307 - 311. [Abstract] [Full Text]