A peptide vaccine that prevents experimental autoimmune myasthenia gravis by specifically blocking T cell help.
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.
Araga
S
S
Department of Physiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Xu
L
L
Nakashima
K
K
Villain
M
M
Blalock
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000517:prevention & control*; D010455:Peptides / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*
D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D011950:Receptors, Cholinergic; D014612:Vaccines; D004247:DNA