Use of complementary peptides and their antibodies in B-cell-mediated autoimmune disease: prevention of experimental autoimmune myasthenia gravis with a peptide vaccine.
We have developed and describe a new method of altering B-cell-mediated autoimmune diseases by induction of anti-idiotypic (Id) antibodies (Abs) by immunization with complementary peptides. Specifically, a peptide denoted RhCA 67-16 encoded by RNA complementary to RNA for the Torpedo acetylcholine receptor (AChR) main immunogenic region, AChR 61-76, was tested in the Lewis rat model of experimental autoimmune myasthenia gravis (EAMG). Immunization with RhCA 67-16 induced monoclonal and polyclonal anti-Id Ab against Abs to Torpedo AChR 61-76. RhCA 67-16 antisera inhibited AChR binding by AChR-specific Abs. In addition, a mAb to RhCA 67-16 (denoted TCM 240) recognized two well known EAMG-causing mAbs, 6 and 35. TCM 240, but not a control mAb F28C, inhibited mAb 6 binding to Torpedo AChR 67-76 peptide. mAb 35 binding to TCM 240 was inhibited by native Torpedo AChR as well as by RhCA 67-16. In in vivo experiments, immunization with a RhCA 67-16 keyhole limpet hemacyanin (KLH) conjugate blocked the development of EAMG after challenge with native Torpedo AChR (25% disease incidence versus 90% in the controls). This new approach may provide a novel therapy for MG and perhaps other B-cell-mediated autoimmune disorders through the induction of anti-Id Abs with complementary peptide antigens.
Araga
S
S
Department of Physiology and Biophysics, University of Alabama, Birmingham 35294.
Blalock
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000517:prevention & control*; D010455:Peptides / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology* / Q000302:isolation & purification; D014101:Torpedo; D014614:Vaccines, Synthetic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D010455:Peptides; D011950:Receptors, Cholinergic; D014614:Vaccines, Synthetic