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Further Characterization of Immunomodulation by a Monoclonal Antibody against Streptococcus mutans Antigen P1

机译:抗变形链球菌抗原P1单克隆抗体的免疫调节的进一步表征。

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We demonstrated previously that mucosal immunization of mice with Streptococcus mutans coated with the monoclonal antibody (MAb) 6-11A directed against the major surface adhesin protein P1 results in changes in the amount, isotype distribution, and specificity of serum antibodies compared with animals immunized with bacteria only. We now show that the specificity of the mucosal secretory IgA response was also influenced by this MAb. Changes in antibody specificity were associated with changes in biological activity. Serum samples which differed in antibody reactivity with P1 polypeptides generated by partial digestion with N-chlorosuccinimide but not in isotype distribution or overall reactivity with S. mutans or intact P1 demonstrated a statistically significant difference in the ability to inhibit bacterial adherence to salivary-agglutinin-coated hydroxyapatite beads. Serum IgG antibodies against P1 from mice immunized with either S. mutans alone or S. mutans coated with 6-11A were shown to recognize antigenic determinants dependent on the presence of the central proline-rich repeat domain, a segment necessary for the structural integrity of the molecule. However, no statistically significant differences were observed in antibody reactivity with a panel of six partial P1 polypeptides encoded by overlapping spaP subclones, suggesting that the targets of biologically relevant antibodies involve complex epitopes not reconstituted by the recombinant products tested. Lastly, we show that binding of MAb 6-11A to P1 on the surface of S. mutans alters P1's susceptibility to proteolytic digestion. Hence, changes in antigen processing and presentation may contribute to the immunomodulatory effects of this MAb.
机译:我们先前证明,用针对主要表面粘附素蛋白P1的单克隆抗体(MAb)6-11A包裹的变形链球菌小鼠的粘膜免疫可导致其变化,数量,同种型分布和特异性血清抗体与仅用细菌免疫的动物相比。现在我们显示,该MAb也影响粘膜分泌性IgA反应的特异性。抗体特异性的改变与生物学活性的改变有关。血清样品与P1多肽的抗体反应性有所不同,P1多肽的反应性是通过用 N -氯代琥珀酰亚胺部分消化而产生的,但同种型分布或与 S的总体反应性没有差异。变异体或完整的P1在抑制细菌粘附唾液凝集素涂层的羟基磷灰石小珠的能力上具有统计学上的显着差异。用任一种S免疫的小鼠抗P1的血清IgG抗体。变体 S。结果显示,被6-11A包覆的变异子可以识别抗原决定簇,这取决于富含脯氨酸的中央重复域的存在,该区域是分子结构完整性所必需的。但是,与由重叠的 spaP 亚克隆编码的一组六种部分P1多肽的抗体反应性方面,没有观察到统计学上的显着差异,这表明生物学相关抗体的靶标涉及复杂的抗原决定簇,而这些抗原决定簇并未被测试的重组产物重建。最后,我们表明MAb 6-11A与 S表面上的P1结合。变形菌改变了P1对蛋白水解消化的敏感性。因此,抗原加工和呈递的改变可能有助于该MAb的免疫调节作用。

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