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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >IN VIVO EXPRESSION OF A SINGLE VIRAL DNA-BINDING PROTEIN GENERATES SYSTEMIC LUPUS ERYTHEMATOSUS-RELATED AUTOIMMUNITY TO DOUBLE-STRANDED DNA AND HISTONES
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IN VIVO EXPRESSION OF A SINGLE VIRAL DNA-BINDING PROTEIN GENERATES SYSTEMIC LUPUS ERYTHEMATOSUS-RELATED AUTOIMMUNITY TO DOUBLE-STRANDED DNA AND HISTONES

机译：体内单个病毒DNA结合蛋白的表达可产生与双链DNA和组蛋白相关的系统性红斑狼疮相关免疫系统

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摘要

Although the origin of autoimmune antibodies to double-stranded DNA is not known, the variable-region structures of such antibodies indicate that they are produced in response to antigen-selective stimulation, In accordance with this, results from experiments using artificial complexes of DNA and DNA-binding polypeptides for immunizations have indicated that DNA may induce these antibodies. Hence, the immunogenicity of DNA in vivo may depend upon other structures or processes that may render DNA immunogenic. We report that in vivo expression of a single DNA-binding protein, the polyoma virus T antigen, is sufficient to initiate production of anti-double-stranded DNA and anti-histone antibodies but not a panel of other autoantigens, Expression of a mutant, non-DNA-binding T antigen did result in strong production of antibodies to the T antigen, but only borderline levels of antibodies to DNA and no detectable antibodies to histones, Nonexpressing plasmid DNA containing the complete cDNA sequence for T antigen did not evoke such immune responses, indicating that DNA by itself is not immunogenic in vivo, The results represent a conceptual advance in understanding a potential molecular basis for initiation of autoimmunity in systemic lupus erythematosus.
机译：尽管针对双链DNA的自身免疫抗体的来源尚不清楚，但此类抗体的可变区结构表明它们是响应抗原选择性刺激而产生的。据此，这是使用DNA和DNA人工复合物的实验结果用于免疫的DNA结合多肽表明DNA可以诱导这些抗体。因此，体内DNA的免疫原性可能取决于可使DNA具有免疫原性的其他结构或过程。我们报告说，一种DNA结合蛋白，多瘤病毒T抗原的体内表达足以启动抗双链DNA和抗组蛋白抗体的产生，但不能引发其他自身抗原的产生，非DNA结合的T抗原确实会产生针对T抗原的抗体，但只能产生临界水平的针对DNA的抗体，而无法检测到针对组蛋白的抗体。不表达含有T抗原完整cDNA序列的质粒DNA不会引起这种免疫应答，表明DNA本身不是体内免疫原性。该结果代表了在系统性红斑狼疮中引发自身免疫的潜在分子基础的概念性进展。

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