白细胞介素2亲和性配体的筛选

Searching for the Peptide Ligands of Interleukin-2 in Phage-displayed Peptide Library

白细胞介素2(IL-2)及其受体拮抗剂的研究对免疫抑制药物的研制具有重要作用.抗白细胞介素2受体α链中和性单克隆抗体5G1(抗Tac型抗体)能够特异性地阻断IL-2与其受体的结合.因此,5G1可作为目标分子被用来在噬菌体展示肽库中筛选白细胞介素2的亲和性配体.经过4轮亲和性筛选以及5G1亲和活性的测定,6个具有明显5G1亲和活性的噬菌体克隆被发现.DNA序列分析结果显示出,所得到的肽序列具有明显的保守性,即SSFT(L/P)I.该序列与IL-2受体α链没有同源性.因此,SSFT(L/P)I可能模拟了IL-2受体α链上的一个不连续表位(mimotope),为白细胞介素2亲和性配体片段.

Interleukin (IL 2),which is a cytokine secreted by activated T cells, plays important roles in vivo. The abnormal expression of IL 2 and/or its receptor(IL 2R)will result in immunopathological changes, such as autoimmune diseases. Therefore, the antagonists of IL 2/IL 2R are an attractive target for the therapeutic agents of autoimmune diseases and allograft rejection in organ transplant. Interleukin 2 receptor α chain (IL 2Rα) is expressed only on the surface of abnormal T cells in patients with certain leukemias, autoimmune diseases and allograft rejection. Recently, monoclonal antibodies that block the interaction of IL 2 with IL 2Rα have been used in animal model to prevent graft virus host disease (GVHD) and allograft rejection in organ transplanting. However, monoclonal antibody derived from animal could induce an immune response in human. Thus, searching for small molecule antagonists of IL 2/IL 2Rα is very important. Anti Tac monoclonal antibody of IL 2Rα 5G 1 can compete the interaction of IL 2 and IL 2R and therefore was used to screen peptide ligands of IL 2 from a 6 residue phage displayed peptide library. After four rounds of affinity selection and 5G 1 affinity identification, six phages with high 5G 1 affinity were selected out. Of them, a conserved motif SSFT(L/P)I was found. Comparision of this motif with the primary sequence of IL 2Rα showed no homogeneity, which suggests that this peptide may mimic an mimotope on the surface of IL 2Rα.