Characterization of antigen-presenting cells induced by intragastric immunization with recombinant chimeric immunogens constructed from Streptococcus mutans AgI/II and type I or type II heat-labile enterotoxins.
Characterization of antigen-presenting cells induced by intragastric immunization with recombinant chimeric immunogens constructed from Streptococcus mutans AgI/II and type I or type II heat-labile enterotoxins.
复制标题
使用由变形链球菌 AgI/II 和 I 型或 II 型不耐热肠毒素构建的重组嵌合免疫原进行胃内免疫诱导的抗原呈递细胞的表征。
DOI：
10.1111/j.2041-1014.2011.00608.x
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发表时间：
2011
影响因子：
3.7
通讯作者：
Russell,MW
中科院分区：
文献类型：
--
作者：
Zhao,W;Zhao,Z;Russell,MW
胃内（i.g.）用由变形链球菌表面抗原AgI/II的唾液结合区（SBR）和肠细菌不耐热肠毒素的A2/B亚基构建的重组嵌合蛋白免疫已成功用于诱导抗变形链球菌的唾液和循环抗体，其具有抗龋齿的保护潜力。为了研究这些疫苗构建体的作用模式，将小鼠i.g.用SBR和霍乱毒素（CT）或大肠杆菌的II型肠毒素LT-IIa和LT-IIb构建的嵌合蛋白质。通过流式细胞术表征派伊尔集合淋巴结（PP）和肠系膜淋巴结（MLN）中的抗原呈递细胞（APC）。与单独用SBR免疫相比，嵌合蛋白SBR-LTIIaA 2/B和SBR-LTIIbA 2/B增加PP中B细胞和巨噬细胞的数量，减少MLN中B细胞的数量，而SBR-CTA 2/B减少PP和MLN中B细胞和巨噬细胞的数量。用所有三种嵌合蛋白免疫导致MHC II类分子和共刺激受体CD 40、CD 80和CD 86的上调，特别是在PP中的树突状细胞上以及在MLN中的APC上。这些结果为增强嵌合蛋白诱导的免疫应答提供了分子基础，与未偶联抗原相比，并为基于CT或II型肠毒素的嵌合蛋白的差异应答提供了分子基础。
Intragastric (i.g.) immunization with recombinant chimeric proteins constructed from the saliva‐binding region (SBR) ofStreptococcus mutanssurface antigen AgI/II and the A2/B subunits of enterobacterial heat‐labile enterotoxins has been successfully used to induce salivary and circulating antibodies againstS. mutansthat have protective potential against dental caries. To investigate the mode of action of these vaccine constructs, mice were immunized i.g. with chimeric proteins constructed from SBR and cholera toxin (CT) or the type II enterotoxins ofEscherichia coli, LT‐IIa and LT‐IIb. Antigen‐presenting cells (APC) in Peyer’s patches (PP) and mesenteric lymph nodes (MLN) were characterized by flow cytometry. Compared with immunization with SBR alone, chimeric proteins SBR‐LTIIaA2/B and SBR‐LTIIbA2/B increased the number of B cells and macrophages in PP and diminished B cell numbers in MLN, whereas SBR‐CTA2/B diminished the numbers of B cells and macrophages in PP and MLN. Immunization with all three chimeric proteins led to upregulation of MHC class II molecules and co‐stimulatory receptors CD40, CD80, and CD86 especially on dendritic cells in PP and also on APC in MLN. The results provide a molecular basis for the enhanced immune responses induced by chimeric proteins compared with uncoupled antigen, and for differential responses to chimeric proteins based on CT or type II enterotoxins.