标题：Epitope-specific suppression of antibody response in experimental autoimmune myasthenia gravis by a monomethoxypolyethylene glycol conjugate of a myasthenogenic synthetic peptide
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1992
卷号：89
期号：13
页码：5852-5856
DOI：10.1073/pnas.89.13.5852
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
