Induction of anti-DNA antibody with DNA-peptide complexes
Induction of anti-DNA antibody with DNA-peptide complexes
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DOI：
10.1093/intimm/12.11.1569
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发表时间：
2000-11-01
影响因子：
4.4
通讯作者：
Marion, TN
中科院分区：
文献类型：
--
作者：
Desai, DD;Marion, TN
自身免疫小鼠中自发的抗DNA抗体具有由抗原特异性、克隆选择性B细胞刺激产生的抗体的特征。体细胞衍生的抗体可变区结构在自发抗DNA抗体中反复出现的性质表明DNA或DNA-蛋白质复合物可能为自身免疫性抗DNA抗体提供抗原刺激。以前，我们已经证明，天然哺乳动物DNA与免疫原性的DNA结合肽Fus 1克氏锥虫复合物可以诱导抗DNA抗体在小鼠中遗传上不容易患自身免疫性疾病。诱导的抗DNA抗体具有与自身免疫性抗DNA抗体相似的特异性、结构和免疫病理学功能。本实验旨在进一步表征对DNA-肽复合物的免疫应答。不同品系小鼠对DNA-Fus 1免疫的抗体应答存在相当大的差异。范围从C57 BL/6小鼠中几乎无反应到NZW小鼠中最稳健的反应。从T.衍生Fus 1的Cruzi（TCEP）蛋白作为DNA的免疫原性载体同样发挥作用。尽管抗Fus 1和抗TCEP反应非常强，但抗DNA反应通常较弱。结果进行了讨论相对于对照作用的T细胞的帮助和外周B细胞的耐受性，在控制免疫和自身免疫抗体反应的DNA。
Spontaneous anti-DNA antibodies in autoimmune mice have the characteristics of antibodies produced by antigen-specific, clonally selective B cell stimulation. The nature of the somatically derived antibody variable region structures recurrent among spontaneous anti-DNA antibodies suggests that DNA or DNA-protein complexes may provide the antigenic stimulus for autoimmune anti-DNA antibody. Previously we have demonstrated that native mammalian DNA in complexes with an immunogenic DNA-binding peptide Fus1 from Trypanosoma cruzi can induce anti-DNA antibody in mice not genetically prone to autoimmune disease. The induced anti-DNA has similar specificity, structure and immunopathological function as autoimmune anti-DNA. The present experiments were designed to further characterize the immune response to DNA-peptide complexes. There was considerable variation in the antibody responses of mice from different strains to DNA-Fus1 immunizations. The range was from virtually no response in C57BL/6 mice to most robust responses in NZW mice. The full-length 52 amino acid carboxy-extension protein of ubiquitin (CEP) in T. cruzi (TCEP) protein from which Fus1 was derived functions equally well as an immunogenic carrier for DNA. Anti-DNA responses were generally weak even though anti-Fus1 and anti-TCEP responses were very strong. The results are discussed with respect to the contrasting roles of T cell help and peripheral B cell tolerance in controlling immune and autoimmune antibody responses to DNA.