Vié H, Gauthier T, Breathnach R, Bonneville M, Godard A, Dietrich J, Karam G, Gesnel M C, Peyrat M A, Jacques Y, Soulillou J P
Institut National de la Santé et de la Recherche Médicale (U.211), Unité de Recherche sur les Effecteurs Lymphocytaires, Nantes, France.
Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11337-41. doi: 10.1073/pnas.89.23.11337.
We have constructed a hybrid cDNA coding for a fusion protein between human interleukin 2 and a truncated heavy chain from human immunoglobulin M. The protein encoded by this cDNA contains the entire interleukin 2 sequence including its signal peptide, fused at its C terminus to domains 2 to 4 of the immunoglobulin heavy-chain constant region. Cells transfected with the hybrid cDNA secrete multimeric forms of the fusion protein, which bind specifically to cells bearing high-affinity interleukin 2 receptors. This binding leads either to T-cell proliferation or, if complement is added, to T-cell death. Multimeric forms of the fusion protein with a molecular mass above 500 kDa mediate complement-dependent lysis but trigger proliferation inefficiently when compared with forms with a low molecular mass (< 500 kDa). In contrast, the latter efficiently mediate T-cell proliferation without inducing complement-dependent lysis. The high molecular mass fusion proteins could thus constitute valuable tools for specific immunosuppression in humans.
我们构建了一种杂交cDNA，其编码人白细胞介素2与来自人免疫球蛋白M的截短重链之间的融合蛋白。该cDNA编码的蛋白质包含白细胞介素2的完整序列，包括其信号肽，在其C末端与免疫球蛋白重链恒定区的结构域2至4融合。用杂交cDNA转染的细胞分泌融合蛋白的多聚体形式，其特异性结合带有高亲和力白细胞介素2受体的细胞。这种结合要么导致T细胞增殖，要么如果加入补体，则导致T细胞死亡。分子量高于500 kDa的融合蛋白多聚体形式介导补体依赖性裂解，但与低分子量（<500 kDa）的形式相比，引发增殖的效率较低。相反，后者有效地介导T细胞增殖而不诱导补体依赖性裂解。因此，高分子量融合蛋白可能构成人类特异性免疫抑制的有价值工具。
