Epitope-specific suppression of antibody response in experimental autoimmune myasthenia gravis by a monomethoxypolyethylene glycol conjugate of a myasthenogenic synthetic peptide.
A synthetic peptide corresponding to a myasthenogenic region of Torpedo californica acetylcholine (AcCho) receptor (AcChoR) alpha subunit, AcChoR alpha-(125-148), was conjugated to monomethoxypolyethylene glycol (mPEG). Injection of mice with the mPEG-AcChoR alpha-(125-148) conjugate and subsequent immunization with whole Torpedo AcChoR suppressed the development of experimental autoimmune myasthenia gravis (EAMG) by electrophysiological criteria. In anti-AcChoR sera from these animals, the antibody response against unconjugated AcChoR alpha-(125-148) was decreased, while the antibody responses against whole AcChoR and other epitopes were not altered. There were no detectable changes in T-cell proliferation responses to AcChoR alpha-(125-148) or to whole AcChoR in these animals. Prior injections with a "nonsense" peptide-mPEG conjugate had no effect on responses to the subsequent immunization with whole Torpedo AcChoR. The results indicate that the mPEG-AcChoR alpha-(125-148) conjugate has epitope-specific tolerogenicity for antibody responses in EAMG and that the AcChoR alpha-subunit region comprising residues 125-148 plays an important pathophysiological role in EAMG. The epitope-directed tolerogenic conjugates may be useful for future immunotherapies of human myasthenia gravis. The strategy of specific suppression of the antibody response to a predetermined epitope by using a synthetic mPEG-peptide conjugate may prove useful in manipulation and suppression of unwanted immune responses such as autoimmunity and allergy.
Atassi
M Z
MZ
Department of Biochemistry, Baylor College of Medicine, Houston.
Ruan
K H
KH
Jinnai
K
K
Oshima
M
M
Ashizawa
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D000939:Epitopes; D007165:Immunosuppression Therapy / Q000379:methods*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011092:Polyethylene Glycols / Q000737:chemistry; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D000939:Epitopes; D010455:Peptides; D011978:Receptors, Nicotinic; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol