Duggan D B, Mackworth-Young C, Kari-Lefvert A, Andre-Schwartz J, Mudd D, McAdam K P, Schwartz R S
Department of Medicine, Tufts-New England Medical Center, Boston, Massachusetts.
Clin Immunol Immunopathol. 1988 Dec;49(3):327-40. doi: 10.1016/0090-1229(88)90123-7.
The origin of autoantibodies against ubiquitous autoantigens (e.g., single-stranded (SS) DNA, cytoskeletal proteins, mitochondria) is obscure. Patients with lepromatous leprosy have many such autoantibodies in their serum. In order to study the polyspecificities of human autoantibodies expressed during infection with Mycobacterium leprae we prepared human monoclonal antibodies derived from the fusion of peripheral blood lymphocytes of a patient with lepromatous leprosy to the human lymphoblastoid line GM 4672. Hybridomas were tested for binding to a DNAse-treated sonicate of M. leprae and a panel of autoantigens. Of the primary (uncloned) cultures, 14% bound ssDNA, 35% bound M. leprae, 11% bound both M. leprae and ssDNA, and 16% bound to mitochondria. Several also bound to the acetylcholine receptor of Torpedo marmorata. Monoclonal antibodies derived from separate primary cultures revealed similar cross-reactions between several autoantigens and M. leprae. In addition, one antibody was identified which bound to mitochondria and the acetylcholine receptor, and which was recognized by an anti-idiotypic antibody which bears the "internal image" of the acetylcholine receptor. These results suggest that antigenic mimicry may play a role in eliciting autoantibody expression from the immune repertoire.
针对普遍存在的自身抗原（如单链（SS）DNA、细胞骨架蛋白、线粒体）的自身抗体的起源尚不清楚。瘤型麻风患者血清中有许多此类自身抗体。为了研究麻风分枝杆菌感染期间表达的人类自身抗体的多特异性，我们制备了源自一名瘤型麻风患者外周血淋巴细胞与人类淋巴母细胞系GM 4672融合的人单克隆抗体。检测杂交瘤与经DNA酶处理的麻风分枝杆菌超声裂解物和一组自身抗原的结合情况。在原代（未克隆）培养物中，14%与单链DNA结合，35%与麻风分枝杆菌结合，11%既与麻风分枝杆菌又与单链DNA结合，16%与线粒体结合。有几种还与电鳐的乙酰胆碱受体结合。来自不同原代培养物的单克隆抗体显示出几种自身抗原与麻风分枝杆菌之间类似的交叉反应。此外，鉴定出一种抗体，它与线粒体和乙酰胆碱受体结合，并被一种具有乙酰胆碱受体“内影像”的抗独特型抗体识别。这些结果表明，抗原模拟可能在从免疫库中引发自身抗体表达方面起作用。
