A HUMAN AUTOIMMUNE PROTEIN ASSOCIATED WITH U1 RNA CONTAINS A REGION OF HOMOLOGY THAT IS CROSS-REACTIVE WITH RETROVIRAL P30GAG ANTIGEN
A HUMAN AUTOIMMUNE PROTEIN ASSOCIATED WITH U1 RNA CONTAINS A REGION OF HOMOLOGY THAT IS CROSS-REACTIVE WITH RETROVIRAL P30GAG ANTIGEN
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DOI：
10.1016/0092-8674(87)90148-6
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发表时间：
1987-10-23
期刊：
影响因子：
64.5
通讯作者：
KEENE, JD
中科院分区：
文献类型：
--
作者：
QUERY, CC;KEENE, JD
利用结缔组织病患者的自身抗体，从人脑干文库中克隆了一个编码与U1小核核糖核蛋白（snRNP）相关的70 kd蛋白（70 K）的cDNA。cDNA衍生的氨基酸序列含有与鼠白血病病毒组特异性抗原p30 gag的区域同源的23个残基。同源性存在于70 K蛋白的抗原部分，并由核心共有序列ETPEEREERRR定义，其作为串联重复出现在大多数哺乳动物C型逆转录病毒的p30 gag中。抗p30 gag抗体识别重组70 K-LacZ融合蛋白以及U1 snRNP。使用合成肽作为竞争对手，我们证明了该区域的同源性包括免疫交叉反应性的网站。因此，针对U1 snRNP的自身抗体通过用p30 gag免疫来引发。在这些发现的基础上，我们提出了逆转录病毒在启动自身免疫中的作用。
cDNA encoding a 70 kd protein (70K) associated with U1 small nuclear ribonucleoprotein (snRNP) was cloned from a human brain-stem library using autoantibodies from patients with connective tissue disease. The cDNA-derived amino acid sequence contains 23 residues homologous to a region of murine leukemia virus group-specific antigen p30gag. The homology resides in an antigenic portion of the 70K protein and is defined by a core consensus sequence, ETPEEREERRR, that occurs as a tandem repeat in p30gag of most mammalian type C retroviruses. Anti-p30gag antibodies recognized a recombinant 70K-LacZ fusion protein as well as U1 snRNPs. Using synthetic peptides as competitors, we demonstrated that the region of homology encompasses the site of immunological cross-reactivity. Thus autoantibodies against U1 snRNPs were elicited by immunization with p30gag. On the basis of these findings, we suggest a role for retroviruses in the initiation of autoimmunity.