Scofield R H, Harley J B
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3343-7. doi: 10.1073/pnas.88.8.3343.
The fine specificity of a reference human anti-Ro/SSA autoantibody-containing serum has been analyzed by using sequential overlapping octapeptides from the human 60-kDa Ro/SSA antigen. From preliminary data, the most antigenic octapeptide in the carboxyl-terminal 120 amino acid residues of Ro/SSA shares seven of eight amino acids with the nucleocapsid (N) protein from the Indiana serotype of vesicular stomatitis virus. A sequence comparison of Ro/SSA and N has unexpectedly revealed six small peptides shared by Ro/SSA and N. Fine specificity analysis with 531 octapeptides from the Ro/SSA sequence demonstrates that five of the six shared small peptides are bound by anti-Ro/SSA (P = 0.00017). A more powerful association is not present in 12,476 protein sequences similarly evaluated. In addition, the inclusion of single-residue gaps in Ro/SSA enlarges the sequence similarity of Ro/SSA and N for three of the five small shared antigenic peptides. This additional level of sequence similarity between Ro/SSA and N is unlikely to be the result of chance (P less than 0.0002). While a number of models may explain these data, including independent immune responses to N and Ro/SSA, these results are also consistent with anti-Ro/SSA autoantibodies being the consequence of a specific viral exposure.
通过使用来自人60 kDa Ro/SSA抗原的连续重叠八肽，分析了一种含人抗Ro/SSA自身抗体的参考血清的精细特异性。根据初步数据，Ro/SSA羧基末端120个氨基酸残基中最具抗原性的八肽与水疱性口炎病毒印第安纳血清型的核衣壳（N）蛋白有八个氨基酸中的七个相同。Ro/SSA和N的序列比较意外地发现了Ro/SSA和N共有的六个小肽。用来自Ro/SSA序列的531个八肽进行的精细特异性分析表明，六个共有的小肽中有五个与抗Ro/SSA结合（P = 0.00017）。在同样评估的12,476个蛋白质序列中不存在更强的关联。此外，在Ro/SSA中包含单残基间隙扩大了Ro/SSA和N在五个共有的小抗原肽中的三个的序列相似性。Ro/SSA和N之间这种额外水平的序列相似性不太可能是偶然的结果（P小于0.0002）。虽然许多模型可以解释这些数据，包括对N和Ro/SSA的独立免疫反应，但这些结果也与抗Ro/SSA自身抗体是特定病毒暴露的结果一致。
