The importance of the location of antibody binding on the M6 protein for opsonization and phagocytosis of group A M6 streptococci.
The importance of the location of antibody binding on the M6 protein for opsonization and phagocytosis of group A M6 streptococci.
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DOI：
10.1084/jem.167.3.1114
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发表时间：
1988-03-01
期刊：
影响因子：
--
通讯作者：
Fischetti VA
中科院分区：
文献类型：
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作者：
Jones KF;Fischetti VA
在19个抗本地A群链球菌M6蛋白的单抗中，有一个在杀菌试验中被证明对6型生物无效。根据先前对M6分子表位位点的了解，选择了抗音抗体和三种非抗音抗体进行同型和补体固定研究。单抗3B8 （IgG3）的表位位于分子的nh2末端高变区（远离细胞），单抗10B6 （IgG2a）和10F5 （IgG2b）都位于分子的保守中心区域，都是固定补体，而10A11 （IgG1）没有。尽管单克隆抗体10B6和10F5都具有相似的补体固定能力、结合滴度和表位表面暴露，但只有3B8单克隆抗体是阴性的。对代表M6蛋白不同区域的合成肽产生的抗体分析表明，尽管来自其他区域的肽产生的抗体对天然M6蛋白具有高结合滴度，并且具有与完整链球菌细胞结合的能力，但只有氨基末端肽（残基1-21）能够引发反对抗体。这些结果不仅支持观察到的调理抗体的类型特异性，而且清楚地指出，相对于抗体在M6链球菌的调理和吞噬方面的实际功能能力，抗体结合在M分子上的位置非常重要。这些结果可能强调了最近观察到的补体因子H在M蛋白抗吞噬活性中的作用。
One of 19 mAbs against the native group A streptococcal M6 protein proved opsonic for type 6 organisms in a bactericidal assay. The opsonic and three nonopsonic antibodies were selected for isotype and complement fixation studies based on previous knowledge of their epitope site on the M6 molecule. While mAb 3B8 (IgG3), whose epitope is in the NH2-terminal hypervariable region of the molecule (distal from the cell), and mAbs 10B6 (IgG2a) and 10F5 (IgG2b), both located in the conserved central region of the molecule, all fix complement, 10A11 (IgG1) did not. Only mAb 3B8 was opsonic despite the fact that mAbs 10B6 and 10F5 both exhibited similar complement-fixing capacity, binding titer, and surface exposure of epitopes. Analysis of antibodies raised against synthetic peptides representing various regions of the M6 protein showed that only the amino-terminal peptide (residues 1-21) was capable of eliciting opsonic antibodies, despite the fact that peptides from other areas produced antibodies with high-binding titers to the native M6 protein and also with the ability to bind to intact streptococcal cells. These results not only support the observed type specificity of opsonic antibodies, but also clearly point to the importance of the location of antibody binding on the M molecule relative to the actual functional capacity of the antibody with respect to the opsonization and phagocytosis of M6 streptococci. These results may underscore the recently observed role of complement Factor H in the antiphagocytic activity of the M protein.