Huber S, Polgar J, Moraska A, Cunningham M, Schwimmbeck P, Schultheiss P
Department of Pathology, University of Vermont, Burlington 05405.
Scand J Infect Dis Suppl. 1993;88:67-78.
Three monoclonal antibodies (mAB) to group A streptococcus M5 serotype (mAB 36.2.2, 49.8.9 and 54.2.8) cross-reactivity bind to various heart antigens (including myosin, tropomyosin and vimentin) and neutralize a myocarditic variant of coxsackievirus B-3 (Nancy) (CVB3). The existence of shared antigenic epitopes between the two distinct infectious agents and the heart implies that antigenic mimicry may form the foundation of the autoimmune response. Plaque purified variants of CVB3 were isolated with these streptococcal mAB. The wild-type virus (H3) and the virus variants made with mABs 36.2.2 (H3-36) and 54.2.8 (H3-54) caused significant myocarditis in Balb/c (H-2d) mice, but not in CBA (H-2k) animals. The virus variant made with mAB 49.8.9 (H3-49) caused myocarditis in CBA, but not in Balb/c mice. No significant differences in virus concentrations in the heart were detected with any of the virus variants. Cytolytic activity of mesenteric lymph node cells generally correlated to the severity of myocarditis in the infected animals. Using overlapping synthetic peptides of the CVB3 VP1 protein, mAB 49.8.9 was shown to bind preferentially peptides 6, 8, 11, and 12. T lymphocytes from H3 infected mice proliferated to VP1 peptides 1, 3, 9, 13, 14, and 21. To determine whether immunity to specific peptides could affect CVB3 pathogenicity, Balb/c mice were immunized with VP1 peptides 1, 3, 6, 13, 14 and 21 in complete Freund's adjuvant (CFA) then infected with 5 x 10(4) PFU CVB3 14 days later. Pre-immunization of animals with (a) peptide 1 resulted in a significant decrease in virus titers in the heart, (b) peptides 3, 13 and 21 increased animal mortality and lymphocyte mediated cytotoxicity to uninfected cardiocyte targets, and (c) peptides 3 and 21 resulted in significant increases in myocarditis compared to animals given virus without pre-immunization.
三种针对A群链球菌M5血清型的单克隆抗体（mAB 36.2.2、49.8.9和54.2.8）具有交叉反应性，可与多种心脏抗原（包括肌球蛋白、原肌球蛋白和波形蛋白）结合，并中和柯萨奇病毒B-3（Nancy株）（CVB3）的一种致心肌炎变异株。这两种不同的感染因子与心脏之间存在共同的抗原表位，这意味着抗原模拟可能构成自身免疫反应的基础。用这些链球菌单克隆抗体分离出了CVB3的噬斑纯化变异株。野生型病毒（H3）以及用单克隆抗体36.2.2（H3-36）和54.2.8（H3-54）制备的病毒变异株在Balb/c（H-2d）小鼠中引起了显著的心肌炎，但在CBA（H-2k）动物中未引起。用单克隆抗体49.8.9（H3-49）制备的病毒变异株在CBA小鼠中引起了心肌炎，但在Balb/c小鼠中未引起。未检测到任何病毒变异株在心脏中的病毒浓度有显著差异。肠系膜淋巴结细胞的溶细胞活性通常与受感染动物心肌炎的严重程度相关。使用CVB3 VP1蛋白的重叠合成肽，发现单克隆抗体49.8.9优先结合肽6、8、11和12。来自H3感染小鼠的T淋巴细胞对VP1肽1、3、9、13、14和21发生增殖反应。为了确定对特定肽的免疫是否会影响CVB3的致病性，将Balb/c小鼠用VP1肽1、3、6、13、14和21在完全弗氏佐剂（CFA）中免疫，然后在14天后用5×10⁴ 空斑形成单位（PFU）的CVB3感染。用（a）肽1对动物进行预免疫导致心脏中的病毒滴度显著降低，（b）肽3、13和21增加了动物死亡率以及淋巴细胞介导的对未感染心肌细胞靶标的细胞毒性，并且（c）与未进行预免疫就感染病毒的动物相比，肽3和21导致心肌炎显著增加。
