Cunningham M W, Antone S M, Gulizia J M, McManus B M, Fischetti V A, Gauntt C J
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1320-4. doi: 10.1073/pnas.89.4.1320.
The development of autoimmunity in certain instances is related to infectious agents. In this report, cytotoxic monoclonal antibodies (mAbs) that recognize epitopes on both enteroviruses and the bacterium Streptococcus pyogenes are described. Murine anti-streptococcal mAbs that were crossreactive with streptococcal M protein, human cardiac myosin, and other alpha-helical coiled-coil molecules were found to neutralize coxsackieviruses B3 and B4 or poliovirus type 1. The viral-neutralizing anti-streptococcal mAbs were also cytotoxic for heart and fibroblast cell lines and reacted with viral capsid proteins on a Western immunoblot. Alignment of amino acid sequences shared between streptococcal M protein, coxsackie-virus B3 capsid protein VP1, and myosin revealed 40% identity in a 14- to 15-amino acid overlap. Synthetic peptides containing these sequences blocked mAb reactivity with streptococcal M protein. The data show that antibodies against alpha-helical structures of bacterial and viral antigens can lead to cytotoxic reactions and may be one mechanism to explain the origin of autoimmune heart disease.
在某些情况下，自身免疫的发展与感染因子有关。在本报告中，描述了识别肠道病毒和化脓性链球菌抗原表位的细胞毒性单克隆抗体（mAb）。发现与链球菌M蛋白、人心脏肌球蛋白和其他α-螺旋卷曲螺旋分子交叉反应的鼠抗链球菌mAb可中和柯萨奇病毒B3和B4或1型脊髓灰质炎病毒。病毒中和性抗链球菌mAb对心脏和成纤维细胞系也具有细胞毒性，并在Western免疫印迹上与病毒衣壳蛋白发生反应。链球菌M蛋白、柯萨奇病毒B3衣壳蛋白VP1和肌球蛋白之间共享的氨基酸序列比对显示，在14至15个氨基酸的重叠区域中有40%的同一性。含有这些序列的合成肽阻断了mAb与链球菌M蛋白的反应。数据表明，针对细菌和病毒抗原α-螺旋结构的抗体可导致细胞毒性反应，可能是解释自身免疫性心脏病起源的一种机制。
