Immunogenic epitopes of the p55 chain of the IL-2 receptor. Relationships to high-affinity IL-2 binding and modulation of the p55 chain.
Immunogenic epitopes of the p55 chain of the IL-2 receptor. Relationships to high-affinity IL-2 binding and modulation of the p55 chain.
复制标题
IL-2 受体 p55 链的免疫原性表位。
DOI：
10.1097/00007890-199003000-00021
复制
发表时间：
1990
期刊：
影响因子：
6.2
通讯作者：
Colvin,RB
中科院分区：
文献类型：
--
作者：
Wong,JT;Schott,E;Sabga,EM;Kielpinski,GG;Colvin,RB
使用单克隆抗体确定 IL-2 受体 p55 链上的表位与高亲和力 IL-2 结合之间的关系。用转染人 p55 cDNA 的鼠 L 细胞对小鼠进行免疫接种，诱导产生针对 IL-2 受体人 P55 链的五种单克隆抗体。由于p55链是这些细胞上表达的唯一人类抗原，因此产生的所有抗人MAB都针对该分子。这些抗体用于绘制 p55 链上的表位图并确定它们与高亲和力 IL-2 结合的关系。对这些 MAB 和大量其他抗 p55 MAB 进行的广泛流式细胞术研究揭示了三种主要的竞争模式。 I 型 MAB 与抗 Tac 广泛竞争，但不与其他组的抗体竞争。 II 型 MAB 不会阻断抗 Tac，但会阻断 7E11。 III 型 MAB 不会阻断 I 型或 II 型抗体。高亲和力条件下的 125 I-IL2 竞争研究表明，I 型和 II 型 MAB 抑制 IL-2 结合。 III 型 MAB 可分为两个亚组，一组抑制 IL-2 结合，另一组则不抑制。这些数据表明，人 p55 链上至少有 4 个不同的免疫原性表位，其中 3 个表位与 IL-2 结合相关。 Scatchard 图上 Kd 的变化表明竞争成分表明所有三个表位都接近或属于 p55 链的 IL-2 结合位点。由这些抗体诱导的高亲和力 IL-2 受体数量较少证明，非竞争性成分表明相同的表位也靠近 p55 和 p70 链之间形成高亲和力受体的相互作用位点。这些研究表明，p55 和 p70 链之间的 IL-2 结合位点和相互作用位点靠近或相同。调节研究表明，一种 II 型抗体 (7E11) 在没有 IL2 和 p70 链的情况下调节 p55 链，从而揭示 p55 链的调节可以通过主动过程发生，而不仅仅是在 IL-2 结合时由 p70 链被动地共同调节。单独调节 p55 链对 IL-2 反应性 T 淋巴细胞没有增殖作用。这种抗体依赖性调节可能可用于将毒素递送至活化的淋巴细胞。
Monoclonal antibodies were used to determine the relationships between epitopes on the p55 chain of the IL-2 receptor and high-affinity IL-2 binding. Five monoclonal antibodies to the human P55 chain of the IL-2 receptor were induced by immunizing mice with murine L cells that were transfected with human p55 cDNA. Since the p55 chain is the only human antigen expressed on these cells, all antihuman MABs thus generated were directed against this molecule. These antibodies were used to map epitopes on the p55 chain and determine their relationship to high-affinity IL-2 binding. Extensive flow cytometric studies with these MABs and a large panel of other anti-p55 MABs revealed three major patterns of competition. Type I MABs compete with anti-Tac extensively but not with antibodies of other groups. Type II MABs do not block anti-Tac but do block 7E11. Type III MABs do not block either type I or type II antibodies. 125 I-IL2 competition studies under high-affinity conditions revealed that types I and II MABs inhibit IL-2 binding. Type III MABs can be resolved into two subgroups, one that inhibits IL-2 binding and one that does not. Together these data suggest that there are at least four distinct immunogenic epitopes on the human p55 chain, with three epitopes related to IL-2 binding. The competitive component evident by a change in Kd on the Scatchard plots suggests that all three epitopes are close to or part of the IL-2-binding site of the p55 chain. The noncompetitive component, as evidenced by the lower number of high-affinity IL-2 receptors induced by these antibodies, suggests that the same epitopes are also close to the site (s) of interaction between the p55 and p70 chains to form the high-affinity receptor. These studies indicated that the IL-2-bind-ing site and site of interaction between the p55 and p70 chains are close together or identical. Modulation studies revealed that one type II antibody (7E11) modulates the p55 chain in the absence of IL2 and the p70 chain, thus revealing that modulation of the p55 chain can occur by an active process, and not merely passively comodulate by the p70 chain upon IL-2 binding. Modulation of the p55 chain alone has no proliferative effect on IL-2-responsive T lymphoblasts. Potentially this antibody-dependent modulation may be used to deliver toxin to activated lymphocytes.