Hartwig U F, Fleischer B
First Department of Medicine, University of Mainz, Germany.
Int Immunol. 1993 Aug;5(8):869-75. doi: 10.1093/intimm/5.8.869.
Streptococcal pyrogenic exotoxin A (SPEA) is an important pathogenicity factor of group A streptococci. It is a member of the family of 'superantigens' produced by Staphylococcus aureus and Streptococcus pyogenes, and its T lymphocyte stimulating activity is involved in the pathogenesis of certain diseases caused by pyogenic streptococci. In this study we have generated nine mutant SPEA molecules by substituting amino acids in the regions of homology between different streptococcal and staphylococcal superantigens. An additional mutant was created by deletion of the 10 N-terminal amino acids. The mutants were expressed as fusion proteins. Several mutations led to a loss of function due to a loss of class II-binding activity. Such loss mutations did not cluster to a certain region of the SPEA molecule. Rather, even a substitution of neighboring amino acids had opposite effects. None of the loss mutations affected the binding of neutralizing mAb and all loss mutants could be precipitated in Ouchterlony tests by a polyclonal anti-SPEA serum. We conclude that the functional activities of SPEA, and probably of other superantigens as well, cannot be attributed to a defined region of the molecule.
链球菌致热外毒素A（SPEA）是A组链球菌的一种重要致病因子。它是金黄色葡萄球菌和化脓性链球菌产生的“超抗原”家族的成员，其T淋巴细胞刺激活性参与了化脓性链球菌引起的某些疾病的发病机制。在本研究中，我们通过替换不同链球菌和葡萄球菌超抗原之间同源区域的氨基酸，产生了9个突变的SPEA分子。通过缺失10个N端氨基酸又产生了一个额外的突变体。这些突变体被表达为融合蛋白。由于II类结合活性丧失，一些突变导致功能丧失。这种功能丧失突变并不聚集在SPEA分子的特定区域。相反，即使相邻氨基酸的替换也有相反的效果。所有功能丧失突变均不影响中和单克隆抗体的结合，并且所有功能丧失突变体在免疫双扩散试验中均可被多克隆抗SPEA血清沉淀。我们得出结论，SPEA以及可能其他超抗原的功能活性不能归因于分子的特定区域。
