Abstract
A synthetic peptide corresponding to a myasthenogenic region of Torpedo californica acetylcholine (AcCho) receptor (AcChoR) α subunit, AcChoRα-(125-148), was conjugated to monomethoxypolyethylene glycol (mPEG). Injection of mice with the mPEG-AcChoRα-(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 AcChoRα-(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 AcChoRα-(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-AcChoRα-(125-148) conjugate has epitope-specific tolerogenicity for antibody responses in EAMG and that the AcChoR α-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.
Original language | English (US) |
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Pages (from-to) | 5852-5856 |
Number of pages | 5 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 89 |
Issue number | 13 |
DOIs | |
State | Published - Jul 1 1992 |
Keywords
- Acetylcholine receptor
- Electromyography
- Immune system manipulation
- T cell
- Tolerogen-peptide conjugate
ASJC Scopus subject areas
- General