Rhodes G H, Valbracht J R, Nguyen M D, Vaughan J H
Department of Medicine and Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla, 92093-0663, USA.
J Autoimmun. 1997 Oct;10(5):447-54. doi: 10.1006/jaut.1997.9996.
In infectious mononucleosis (IM), anti-EBNA-1 antibodies are produced which cross-react with multiple normal human proteins. The cross-reactions can be inhibited with synthetic peptides representing the glycine/alanine repeat in EBNA-1, which implies that the cross-reactivity is due to anti-gly/ala antibodies that cross-react with host proteins containing configurations like those in the EBNA-1 repeat. Here we report the isolation of five gene fragments from a Raji B lymphocyte cDNA library encoding peptides reactive with autoantibodies in an IM serum. One of these, p542, encodes a glycine rich 28-mer which constitutes its cross-reactive epitope, as shown elsewhere. By Northern blots, p542 was identifiable in three B lymphocyte lines, a T cell line, and an epithelial cell line. In a search of the GenBank for proteins with sequence similarity to p542, we found a high degree of identity with the mid- and 3' terminal regions of the recently published mouse gene, Raly, which encodes a protein with the structure of a heterogeneous nuclear ribonuclear protein (hnRNP). We confirmed by anchored RT-PCR our presumption that the 5' sequences of p542 also have a high degree of identity with Raly, including presence of RNA binding motifs characteristic of hnRNPs. There was also sequence homology with human hnRNP C2. From these observations and our previous studies, we conclude that the autoantigen for one of the cross-reactive autoantibodies generated during immune responses to the Epstein Barr virus, anti-p542, is probably an hnRNP.
在传染性单核细胞增多症(IM)中,会产生与多种正常人蛋白质发生交叉反应的抗EBNA-1抗体。这些交叉反应可用代表EBNA-1中甘氨酸/丙氨酸重复序列的合成肽来抑制,这表明交叉反应性是由于抗甘氨酸/丙氨酸抗体与含有类似EBNA-1重复序列结构的宿主蛋白质发生交叉反应所致。在此,我们报告从Raji B淋巴细胞cDNA文库中分离出五个基因片段,它们编码的肽可与IM血清中的自身抗体发生反应。其中一个片段p542编码一个富含甘氨酸的28肽,如在其他地方所示,该肽构成其交叉反应表位。通过Northern印迹法,在三种B淋巴细胞系、一种T淋巴细胞系和一种上皮细胞系中可鉴定出p542。在GenBank中搜索与p542具有序列相似性的蛋白质时,我们发现它与最近发表的小鼠基因Raly的中部和3'末端区域具有高度同一性,Raly编码一种具有不均一核核糖核蛋白(hnRNP)结构的蛋白质。我们通过锚定RT-PCR证实了我们先前的推测,即p542的5'序列也与Raly具有高度同一性,包括存在hnRNPs特有的RNA结合基序。它与人hnRNP C2也存在序列同源性。基于这些观察结果和我们之前的研究,我们得出结论,在针对爱泼斯坦-巴尔病毒的免疫反应中产生的一种交叉反应性自身抗体的自身抗原,即抗p542,可能是一种hnRNP。