Moore M D, Cannon M J, Sewall A, Finlayson M, Okimoto M, Nemerow G R
Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, California 92037.
J Virol. 1991 Jul;65(7):3559-65. doi: 10.1128/JVI.65.7.3559-3565.1991.
The extracellular domain of CR2, the Epstein-Barr virus (EBV)/C3d receptor of B lymphocytes, contains 15 or 16 tandemly arranged short consensus repeat elements (SCR). Recombinant CR2 proteins containing SCR 1 and 2 fused to Staphylococcus aureus protein A (PA-CR2) and to murine complement factor H SCR 20 (CR2FH) were expressed in Escherichia coli and in insect cells, respectively. These recombinant CR2 molecules retained functional activity as indicated by their ability to bind to C3dg in an enzyme-linked immunosorbent assay and to inhibit EBV gp350/220 binding to B cells. PA-CR2 and CR2FH were as efficient in blocking EBV gp350/220 binding as the full-length CR2 extracellular domain, indicating that the first two SCR of CR2 contain the majority of the ligand binding activity of the receptor. PA-CR2 and CR2FH inhibited EBV-induced B-cell proliferation in vitro and blocked the development of EBV-induced lymphoproliferative disease in severe combined immunodeficient mice reconstituted with human lymphocytes. These studies indicate that soluble forms of truncated CR2 proteins may have potential therapeutic value in the treatment of EBV-induced lymphoproliferative disorders in humans that involve viral replication.
CR2的胞外结构域是B淋巴细胞的爱泼斯坦-巴尔病毒（EBV）/C3d受体，包含15或16个串联排列的短共有重复元件（SCR）。分别在大肠杆菌和昆虫细胞中表达了含有与金黄色葡萄球菌蛋白A融合的SCR 1和2的重组CR2蛋白（PA-CR2）以及与小鼠补体因子H SCR 20融合的重组CR2蛋白（CR2FH）。这些重组CR2分子保留了功能活性，这体现在它们在酶联免疫吸附测定中与C3dg结合以及抑制EBV gp350/220与B细胞结合的能力上。PA-CR2和CR2FH在阻断EBV gp350/220结合方面与全长CR2胞外结构域一样有效，表明CR2的前两个SCR包含该受体大部分的配体结合活性。PA-CR2和CR2FH在体外抑制EBV诱导的B细胞增殖，并在用人淋巴细胞重建的严重联合免疫缺陷小鼠中阻断EBV诱导的淋巴增殖性疾病的发展。这些研究表明，截短的CR2蛋白的可溶性形式在治疗涉及病毒复制的人类EBV诱导的淋巴增殖性疾病中可能具有潜在的治疗价值。
