{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T03:08:08Z","timestamp":1779332888045,"version":"3.51.4"},"reference-count":73,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,6,28]],"date-time":"2008-06-28T00:00:00Z","timestamp":1214611200000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:p>The main immunogenic region (MIR), against which half or more of the autoantibodies to acetylcholine receptors (AChRs) in myasthenia gravis (MG) or experimental autoimmune MG (EAMG) are directed, is located at the extracellular end of \u03b11 subunits. Rat monoclonal antibodies (mAbs) to the MIR efficiently compete with MG patient autoantibodies for binding to human muscle AChRs. Antibodies bound to the MIR do not interfere with cholinergic ligand binding or AChR function, but target complement and trigger antigenic modulation. Rat mAbs to the MIR also bind to human ganglionic AChR \u03b13 subunits, but MG patient antibodies do not. By making chimeras of \u03b11 subunits with \u03b17 subunits or ACh binding protein, the structure of the MIR and its functional effects are being investigated. Many mAbs to the MIR bind only to the native conformation of \u03b11 subunits because they bind to sequences that are adjacent only in the native structure. The MIR epitopes recognized by these mAbs are not recognized by most patient antibodies whose epitopes must be nearby. The presence of the MIR epitopes in \u03b11\/\u03b17 chimeras greatly promotes AChR expression and sensitivity to activation. EAMG can be suppressed by treatment with denatured, bacterially expressed mixtures of extracellular and cytoplasmic domains of human \u03b11, \u03b21, \u03b3, \u03b4, and \u025b subunits. A mixture of only the cytoplasmic domains not only avoids the potential liability of provoking formation antibodies to pathologically significant epitopes on the extracellular surface, but also potently suppresses the development of EAMG.<\/jats:p>","DOI":"10.1196\/annals.1405.007","type":"journal-article","created":{"date-parts":[[2008,6,20]],"date-time":"2008-06-20T23:23:28Z","timestamp":1214004208000},"page":"29-41","source":"Crossref","is-referenced-by-count":29,"title":["<i>Myasthenia Gravis and the Tops and Bottoms of AChRs<\/i>"],"prefix":"10.1111","volume":"1132","author":[{"given":"Jon","family":"Lindstrom","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Kuryatov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,6,28]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04708"},{"key":"e_1_2_5_3_2","first-page":"101","volume-title":"Handbook of Experimental Pharmacology","author":"Lindstrom J.","year":"2000"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2007.05935.x"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2006.07.004"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0906-6705.2006.00410.x"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30555"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(200004)23:4<453::AID-MUS3>3.0.CO;2-O"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1485-04.2004"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1159\/000051540"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1101"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608215103"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099420"},{"key":"e_1_2_5_14_2","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nature05371","article-title":"A prokaryotic proton\u2010gated ion channel from the nicotinic acetylcholine receptor family","volume":"445","author":"Bocquet N.","year":"2006","journal-title":"Nature"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.63.2.332"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.105.012419"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.030445"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.027326"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051622798"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-02-00442.1993"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.12.031"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/35077011"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02753"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(04)00115-1"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600828"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(03)74720-1"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn731"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90270-2"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M513222200"},{"key":"e_1_2_5_30_2","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/S0026-895X(24)12167-0","article-title":"Regulation of \u03b14\u03b22 nicotinic receptor desensitization by calcium and protein kinase C","volume":"55","author":"Fenster C.","year":"1999","journal-title":"Mol. 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