Tsudo M, Goldman C K, Bongiovanni K F, Chan W C, Winton E F, Yagita M, Grimm E A, Waldmann T A
Proc Natl Acad Sci U S A. 1987 Aug;84(15):5394-8. doi: 10.1073/pnas.84.15.5394.
There are at least two interleukin 2 (IL-2) binding peptides: one is the Mr 55,000 peptide (p55) reactive with the anti-Tac monoclonal antibody, and the other is a Mr 75,000 non-Tac IL-2 binding peptide (p75). Independently existing Tac or p75 peptides represent low-affinity IL-2 receptors, whereas high-affinity IL-2 receptors are expressed when both peptides are present and associated in a receptor complex. It has long been known that normal large granular lymphocytes (LGL) or leukemic cells from the patients with abnormal expansions of LGL can be activated by IL-2 not only to more-potent natural killer cells but also to effectors of lymphokine-activated killer (LAK) activity, although they do not express the Tac peptide. In the present study, using cross-linking methodology, we found that normal LGL and leukemic LGL from all individuals tested expressed the p75 IL-2 binding peptide but did not express the Tac peptide. These LGL leukemia cells made proliferative responses to IL-2 but required a much higher concentration than that required for the proliferation of normal phytohemagglutinin-stimulated T lymphoblasts that express high-affinity receptors. Furthermore, the addition of IL-2 to Tac-negative LGL leukemic cells augmented transcription of the Tac gene and induced the Tac peptide. Neither the IL-2-induced proliferation nor the up-regulation of Tac gene expression was inhibited by the addition of anti-Tac. These results strongly suggest that the p75 peptide is responsible for IL-2-induced activation of LGL and that the p75 peptide alone can mediate an IL-2 signal. Thus, the p75 peptide may play an important role in the IL-2-mediated immune response not only by participating with the Tac peptide in the formation of the high-affinity receptor complex on T cells but also by contributing to the initial triggering of LGL activation so that these cells become efficient natural killer and lymphokine-activated killer cells.
至少有两种白细胞介素2（IL-2）结合肽：一种是与抗Tac单克隆抗体反应的55,000道尔顿肽（p55），另一种是75,000道尔顿的非Tac IL-2结合肽（p75）。独立存在的Tac或p75肽代表低亲和力IL-2受体，而当两种肽同时存在并在受体复合物中结合时，高亲和力IL-2受体才会表达。长期以来已知，正常大颗粒淋巴细胞（LGL）或LGL异常扩增患者的白血病细胞可被IL-2激活，不仅能成为更强效的自然杀伤细胞，还能成为淋巴因子激活的杀伤（LAK）活性效应细胞，尽管它们不表达Tac肽。在本研究中，我们使用交联方法发现，所有测试个体的正常LGL和白血病LGL均表达p75 IL-2结合肽，但不表达Tac肽。这些LGL白血病细胞对IL-2产生增殖反应，但所需浓度比表达高亲和力受体的正常植物血凝素刺激的T淋巴母细胞增殖所需浓度高得多。此外，向Tac阴性LGL白血病细胞中添加IL-2可增强Tac基因的转录并诱导Tac肽的产生。添加抗Tac均不抑制IL-2诱导的增殖或Tac基因表达的上调。这些结果强烈表明，p75肽负责IL-2诱导的LGL激活，且单独的p75肽就能介导IL-2信号。因此，p75肽可能在IL-2介导的免疫反应中发挥重要作用，不仅通过与Tac肽共同参与T细胞上高亲和力受体复合物的形成，还通过促成LGL激活的初始触发，使这些细胞成为高效的自然杀伤细胞和淋巴因子激活的杀伤细胞。
