Vaughan J H, Valbracht J R, Nguyen M D, Handley H H, Smith R S, Patrick K, Rhodes G H
Department of Medicine, University of California, San Diego, La Jolla 92093-0663.
J Clin Invest. 1995 Mar;95(3):1306-15. doi: 10.1172/JCI117781.
In previous studies of infectious mononucleosis, we found IgM autoantibodies which react with hematopoietic cell antigens. Many of these were inhibited by synthetic glycine/alanine peptides representing the glycine/alanine repeat of Epstein-Barr virus nuclear antigen-1. We have cloned and expressed fragments of genes encoding two of these autoantigens. One gene (p542) encodes a protein containing a glycine-rich 28-mer, which is its chief autoantigenic epitope and which represents a newly identified class of evolutionarily conserved autoepitopes. The other gene (p554) encodes a protein that is not demonstrably cross-reactive with Epstein-Barr virus nuclear antigen-1 or with any other EBV protein, but forms complexes with other proteins. Immunoaffinity-purified anti-p542 and anti-p554 have relatively high binding affinities, as evidenced by inhibition at 10(6)-10(8) M-1, and neither autoantibody showed polyreactivity with other common antigens. The data thus suggest that neither autoantibody is simply an expression of polyclonal B cell activation. We conclude that the two autoantigens stimulate autoantibody synthesis by different mechanisms. One autoantigen shares homology to a viral protein which generates cross-reacting antibodies to the autoantigenic epitope. The other has no recognizable cross-reaction with the infecting pathogen and may become immunogenic through complexing with other proteins.
在先前关于传染性单核细胞增多症的研究中，我们发现了与造血细胞抗原发生反应的IgM自身抗体。其中许多自身抗体可被代表爱泼斯坦-巴尔病毒核抗原-1甘氨酸/丙氨酸重复序列的合成甘氨酸/丙氨酸肽所抑制。我们已经克隆并表达了编码其中两种自身抗原的基因片段。一个基因（p542）编码一种含有富含甘氨酸的28肽的蛋白质，该28肽是其主要自身抗原表位，代表了一类新鉴定的进化保守自身表位。另一个基因（p554）编码的蛋白质与爱泼斯坦-巴尔病毒核抗原-1或任何其他EBV蛋白没有明显的交叉反应，但能与其他蛋白质形成复合物。免疫亲和纯化的抗p542和抗p554具有相对较高的结合亲和力，在10⁻⁶ - 10⁻⁸ M⁻¹浓度下可出现抑制现象，且两种自身抗体均未显示与其他常见抗原发生多反应性。因此，数据表明这两种自身抗体都不是多克隆B细胞活化的简单表现。我们得出结论，这两种自身抗原通过不同机制刺激自身抗体合成。一种自身抗原与一种病毒蛋白具有同源性，该病毒蛋白产生针对自身抗原表位的交叉反应抗体。另一种自身抗原与感染病原体没有可识别的交叉反应，可能通过与其他蛋白质形成复合物而具有免疫原性。
