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Maintenance of antigen-specific immunological memory through variable regions of heavy and light chains of anti-idiotypic antibody

机译:通过抗独特型抗体重链和轻链的可变区维持抗原特异性免疫记忆

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摘要

Immunological memory is characterized by a quick and enhanced immune response after re-exposure to the same antigen. To explain the mechanism involved in generation and maintenance of immunological memory, we had earlier proposed a hypothesis involving the relay of memory by idiotypic and anti-idiotypic B cells. The peptidomimic present in the hypervariable region of anti-idiotypic antibody was hypothesized to carry forward immunological memory. In the present work, we provide evidence supporting a role for the anti-idiotypic antibody in eliciting antigen-specific B-cell and T-cell responses. Employing the idiotypic monoclonal antibody (Ab1) specific for haemagglutinin (H) protein of rinderpest virus, Ab2β was generated, which possesses an internal image of the H protein in the region between amino acids 527 and 556. We demonstrate that antigen-specific memory is perpetuated by immunization with Ab2, as shown by maintenance of antigen-specific T-cell responses upon restimulation in vitro of Ab2 immune splenocytes by antigen-presenting cells expressing H protein or pulsed with H-protein-derived peptides. We have also shown that boosting with antigen-specific anti-idiotypic B cells generates a memory response in antigen-primed mice. Evidence has been provided for the existence of an antigen-specific B-cell idiotypic network in the body that supports the perpetuation of immunological memory as proposed in the relay hypothesis.
机译:免疫记忆的特征是再次暴露于相同抗原后快速而增强的免疫反应。为了解释涉及免疫记忆的产生和维持的机制,我们早些时候提出了一个假设,其中涉及通过独特型和抗独特型B细胞来传递记忆。假定存在于抗独特型抗体的高变区中的肽组可以进行免疫记忆。在目前的工作中,我们提供证据支持抗独特型抗体在引发抗原特异性B细胞和T细胞反应中的作用。利用牛瘟病毒血凝素(H)蛋白特异的独特型单克隆抗体(Ab1),生成了Ab2β,它在氨基酸527和556之间具有H蛋白的内部图像。我们证明抗原特异性记忆是通过用Ab2免疫而永存,如通过表达H蛋白或用H蛋白衍生肽脉冲的抗原呈递细胞在体外对Ab2免疫脾细胞进行再刺激后维持抗原特异性T细胞反应所示。我们还显示,用抗原特异性抗独特型B细胞加强免疫可在抗原引发的小鼠中产生记忆反应。已经提供了证据,证明存在体内的抗原特异性B细胞独特型网络,可以支持免疫假说中提出的永久性免疫记忆。

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