LKM-1 AUTOANTIBODIES RECOGNIZE A SHORT LINEAR SEQUENCE IN P450IID6, A CYTOCHROME-P-450 MONOOXYGENASE
LKM-1 AUTOANTIBODIES RECOGNIZE A SHORT LINEAR SEQUENCE IN P450IID6, A CYTOCHROME-P-450 MONOOXYGENASE
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DOI：
10.1172/jci115443
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发表时间：
1991-10-01
影响因子：
15.9
通讯作者：
JOHNSON, EF
中科院分区：
文献类型：
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作者：
MANNS, MP;GRIFFIN, KJ;JOHNSON, EF
LKM-1 自身抗体与自身免疫性慢性活动性肝炎相关，可识别 P450IID6（一种细胞色素 P-450 单加氧酶）。使用一组在大肠杆菌中表达的 P450IID6 缺失突变体测试了 26 种 LKM-1 抗血清的反应性。 22 个血清识别 P450IID6 的 33 个氨基酸片段，其中 11 个血清识别较短的片段 DPAQPPRD。 PAQPPR 也存在于 1 型单纯疱疹病毒 (HSV-1) 的 IE175 中。通过 ELISA 在测试的 20 份 LKM-1 血清中的 17 份中检测到 HSV-1 蛋白的抗体。使用固定化合成肽 DPAQPPRDC 来纯化 LKM-1 抗体。 HSV-1 感染后，亲和纯化的 LKM-1 自身抗体与 BHK 细胞中的蛋白质在免疫印迹上发生反应。 24 份 LKM-1 血清中的 11 份（包括 3 份识别 DPAQPPRD 的血清）也表现出针对丙型肝炎病毒 (HCV) 蛋白 C100-3 的抗体。亲和纯化的 LKM-1 抗体不识别 C100-3。然而，P450IID6 的免疫阳性 33 个氨基酸片段的部分与推定的 HCV 多蛋白的其他部分之间的部分序列同一性是明显的。 P450IID6 和 HCV 或 HSV-1 蛋白的免疫交叉识别可能有助于 LKM-1 自身抗体的出现。
LKM-1 autoantibodies, which are associated with autoimmune chronic active hepatitis, recognize P450IID6, a cytochrome P-450 monooxygenase. The reactivities of 26 LKM-1 antisera were tested with a panel of deletion mutants of P450IID6 expressed in Escherichia coli. 22 sera recognize a 33-amino acid segment of P450IID6, and 11 of these recognize a shorter segment, DPAQPPRD. PAQPPR is also found in IE175 of herpes simplex virus type 1 (HSV-1). Antibodies for HSV-1 proteins were detected by ELISA in 17 of 20 LKM-1 sera tested. An immobilized, synthetic peptide, DPAQPPRDC, was used to purify LKM-1 antibodies. Affinity purified LKM-1 autoantibodies react on immunoblots with a protein in BHK cells after infection with HSV-1. 11 of 24 LKM-1 sera, including 3 that recognize DPAQPPRD, also exhibit antibodies to the hepatitis C virus (HCV) protein, C100-3. Affinity purified LKM-1 antibodies did not recognize C100-3. However, partial sequence identity was evident between portions of the immunopositive 33-amino acid segment of P450IID6 and other portions of the putative HCV polyprotein. Immune cross-recognition of P450IID6 and HCV or HSV-1 proteins may contribute to the occurrence of LKM-1 autoantibodies.