Adderson E E, Shikhman A R, Ward K E, Cunningham M W
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City 84132, USA.
J Immunol. 1998 Aug 15;161(4):2020-31.
Anti-myosin Abs are associated with inflammatory heart diseases such as rheumatic carditis and myocarditis. In this study, human cross-reactive anti-streptococcal/anti-myosin mAbs 1.C8, 1.H9, 5.G3, and 3.B6, produced from peripheral blood lymphocytes of patients with rheumatic carditis, and mAb 10.2.5, produced from a tonsil, were characterized, and the nucleotide sequences of their V(H) and V(H)L genes were analyzed. Human mAbs 1.C8, 1.H9, 10.2.5, and 3.B6 reacted with human cardiac myosin while mAb 5.G3 did not. The mAbs were strongly reactive with N-acetyl-beta-D-glucosamine, the dominant epitope of the group A streptococcal carbohydrate. mAb 1.H9 was moderately cytotoxic to rat heart cells in vitro in the presence of complement. The anti-myosin mAbs from rheumatic carditis were found to react with specific peptides from the light meromyosin region of the human cardiac myosin molecule. Anti-streptococcal/anti-myosin mAbs from normal individuals reacted with distinctly different light meromyosin peptides. The mAbs were encoded by V(H)3 gene segments V3-8, V3-23, and V3-30 and by the V(H)4 gene segment V4-59. The variable region genes encoding the anti-streptococcal/anti-myosin repertoire were heterogeneous and exhibited little evidence of Ag-driven somatic mutation.
抗肌球蛋白自身抗体与风湿性心内膜炎和心肌炎等炎症性心脏病相关。在本研究中，对由风湿性心内膜炎患者外周血淋巴细胞产生的人交叉反应性抗链球菌/抗肌球蛋白单克隆抗体1.C8、1.H9、5.G3和3.B6，以及由扁桃体产生的单克隆抗体10.2.5进行了特性分析，并对其V(H)和V(H)L基因的核苷酸序列进行了分析。人单克隆抗体1.C8、1.H9、10.2.5和3.B6与人心脏肌球蛋白发生反应，而单克隆抗体5.G3则不发生反应。这些单克隆抗体与A组链球菌碳水化合物的主要表位N-乙酰-β-D-葡萄糖胺有强烈反应。在补体存在的情况下，单克隆抗体1.H9在体外对大鼠心脏细胞有中度细胞毒性。发现来自风湿性心内膜炎的抗肌球蛋白单克隆抗体与人心脏肌球蛋白分子轻酶解肌球蛋白区域的特定肽发生反应。来自正常个体的抗链球菌/抗肌球蛋白单克隆抗体与明显不同的轻酶解肌球蛋白肽发生反应。这些单克隆抗体由V(H)3基因片段V3-8、V3-23和V3-30以及V(H)4基因片段V4-59编码。编码抗链球菌/抗肌球蛋白全套抗体的可变区基因是异质性的，几乎没有抗原驱动的体细胞突变的证据。
