A minimum CR2 binding domain of C3d enhances immunity following vaccination.
A minimum CR2 binding domain of C3d enhances immunity following vaccination.
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C3d 的最小 CR2 结合域可增强疫苗接种后的免疫力。
DOI：
10.1007/0-387-34134-x_17
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发表时间：
2006
影响因子：
--
通讯作者：
Ross,TedM
中科院分区：
文献类型：
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作者：
Bower,JosephF;Ross,TedM
第三（C3）补体成分C3 d的降解产物连接先天性和适应性免疫，并且C3 d与抗原的共价连接增强抗原特异性免疫应答。假设C3 d通过与免疫细胞上的补体受体2（CR2/CD 21）直接相互作用来增强免疫力。然而，对CR2结合重要的C3 d结构域一直存在争议，各种研究得出相互矛盾的结论。此外，C3 d通过CR2激活B细胞的概念也受到质疑，因为缺乏CR2的小鼠在接种疫苗后仍能引起C3 d增强的免疫力。因此，本研究的目的是确定代表C3 d的CR2结合结构域之一的肽是否可以取代整个蛋白质并增强抗原特异性免疫。用HIV-1 gp 120包膜糖蛋白（Envgp 120）单独或与多拷贝鼠C3 d或含有最小CR2结合结构域的28个氨基酸肽（P28）融合接种小鼠（BALB/c）。每种免疫原均由DNA质粒在体内表达或作为纯化的重组蛋白注射。P28肽与Envgp 120的融合增强了体液和细胞介导的免疫应答，其效率与Envgp 120与C3 d缀合相似。与Envgp 120免疫相比，C3 d或P28与Envgp 120的融合引发更高滴度的抗Env特异性抗体，增强所引发抗体的亲合力成熟，并且引发更高数量的IFN-γ和IL-4分泌细胞。这种CR2结合结构域特异性的28个氨基酸的肽可以取代整个C3 d分子并增强免疫力。这些结果表明C3 d的佐剂性质与CR2相互作用相关。
The degradation product of the third (C3) complement component, C3d, links innate and adaptive immunity, and the covalent attachment of C3d to an antigen enhances antigen-specific immune responses. C3d has been hypothesized to enhance immunity by direct interaction with complement receptor 2 (CR2/CD21) on immune cells. However, the domains on C3d important for CR2 binding have been controversial, with various studies reaching contradictory conclusions. In addition, the concept of B-cell activation via CR2 by C3d has been questioned, since mice lacking CR2 still elicit C3d-enhanced immunity following vaccination. Therefore, the goal of this study was to determine if a peptide representing one of the proposed CR2 binding domains of C3d could substitute for the entire protein and enhance antigen-specific immunity. Mice (BALB/c) were vaccinated with the HIV-1 gp120 envelope glycoprotein (Envgp120) alone or fused to multiple copies of the murine C3d or a twenty-eight amino-acid peptide (P28) containing a minimum CR2 binding domain. Each immunogen was expressed from DNA plasmid in vivo or injected as purified recombinant protein. The fusion of the P28 peptide to Envgp120enhanced both humoral and cell-mediated immune responses with similar efficiency as Envgp120conjugated to C3d. The fusion of C3d or P28 to Envgp120elicited higher-titer anti-Env specific antibody, enhanced avidity maturation of the elicited antibody, and elicited higher numbers of IFN-γ and IL-4 secreting cells compared to Envgp120immunizations. This CR2-binding domain specific 28 amino acid peptide can substitute for the entire C3d molecule and enhance immunity. These results indicate that the adjuvant properties of C3d are associated with CR2 interaction.