{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T10:24:05Z","timestamp":1779359045345,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2005,12,9]],"date-time":"2005-12-09T00:00:00Z","timestamp":1134086400000},"content-version":"vor","delay-in-days":4605,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1993,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Anti\u2010liver\u2010kidney microsome type\u20101 antibodies (LKM1), present in sera from a group of patients with autoimmune hepatitis, are directed against P450IID6. Previous work, using cDNA constructions spanning most of the P450IID6 protein defined the main immunogenic site between the amino acids (aa), 254\u2013271 and predicted the presence of other putative immunogenic sites in the molecule. Fusion proteins from new cDNA constructions, spanning so\u2010far\u2010untested regions between aa 1\u2013125 and 431\u2013522, were not recognized by LKM1\u2010positive sera. Synthetic peptides, representing sequences from putative immunogenic regions or previously untested regions, allowed a precise definition of four antigenic sites located between peptides 257\u2013269, 321\u2013351, 373\u2013389 and 410\u2013429, which were recognized, respectively, by 14, 8, 1 and 2 out of 15 LKM1\u2010positive sera tested. The minimal sequence of the main antigenic site (peptide 257\u2010269) recognized by the autoantibody was established to be WDPAQPPRD (peptide 262\u2013270). In addition, deletion and replacement experiments showed that aa 263 (Asp) was essential for the binding of the autoantibody to peptide 262\u2013270. Analysis of the second most frequently recognized peptide between aa 321\u2013351, was performed using peptides 321\u2013339 and 340\u2013351 in competitive inhibition studies. Complete elimination of antibody binding to peptide 321\u2013351 obtained by absorption of both shorter peptides indicated that peptide 321\u2013351 is a discontinuous antigenic site. LKM1\u2010positive sera reacting against peptide 321\u2013351 recognized either both the shorter peptides or just one of them preferentially. Results of the present study suggest that the production of LKM1 antibodies is an antigen\u2010driven, poly\u2010or oligoclonal B cell response. The identification of antigenic sites will allow: (i) the development of specific diagnostic tests and (ii) further studies on the pathogenic value of LKM1 antibodies in autoimmune hepatitis.<\/jats:p>","DOI":"10.1002\/eji.1830230519","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T19:06:21Z","timestamp":1172775981000},"page":"1105-1111","source":"Crossref","is-referenced-by-count":91,"title":["Identification and analysis of cytochrome P450IID6 antigenic sites recognized by anti\u2010liver\u2010kidney microsome type\u20101 antibodies (LKM1)"],"prefix":"10.1002","volume":"23","author":[{"given":"Ana M.","family":"Yamamoto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dani\u00e8le","family":"Cresteil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Odile","family":"Boniface","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7ois F.","family":"Clerc","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,12,9]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(86)80880-0"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840070626"},{"key":"e_1_2_1_4_2","first-page":"331","volume":"15","author":"Rizzetto M.","year":"1973","journal-title":"Clin. 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