Liu K D, Greene W C, Goldsmith M A
Gladstone Institute of Virology and Immunology, School of Medicine, University of California, San Francisco 94141, USA.
Cytokine. 1996 Aug;8(8):613-21. doi: 10.1006/cyto.1996.0082.
Interleukin 2 (IL-2) mediated signalling results from ligand binding and subsequent heterodimerization of IL-2r beta and gamma c. The high-affinity IL-2 receptor (IL-2r) is a heterotrimer comprised of the IL-2r alpha, IL-2r beta and gamma c subunits. Whereas human IL-2 effectively binds to either human or murine lymphocytes, murine IL-2 binds with markedly higher affinity to murine receptor complexes than to human complexes. Using cell lines stably expressing heterotrimeric IL-2r that vary in the species origin of individual subunits, we have demonstrated that IL-2r alpha is primarily responsible for the species specificity of IL-2 binding. Studies of ligand binding to the low affinity receptor demonstrated that IL-2r alpha displays a similar species preference to the heterotrimeric complex. Moreover, differences in ligand binding are reflected in differences in proliferation. A cell line expressing human IL-2r alpha and IL-2r beta along with murine gamma c vigorously proliferated only in response to human IL-2 at low doses, while both human and murine IL-2 stimulated proliferation of a cell line containing murine IL-2r alpha (as well as human IL-2r beta and murine gamma c). Therefore, IL-2r alpha is the chain primarily responsible for the species specificity of ligand binding.
白细胞介素2（IL-2）介导的信号传导源于配体结合以及随后IL-2rβ和γc的异源二聚化。高亲和力白细胞介素2受体（IL-2r）是一种由IL-2rα、IL-2rβ和γc亚基组成的异源三聚体。人IL-2能有效结合人或鼠淋巴细胞，而鼠IL-2与鼠受体复合物的结合亲和力明显高于与人复合物的结合亲和力。利用稳定表达异源三聚体IL-2r且各亚基物种来源不同的细胞系，我们证明了IL-2rα主要负责IL-2结合的物种特异性。对配体与低亲和力受体结合的研究表明，IL-2rα对异源三聚体复合物表现出类似的物种偏好。此外，配体结合的差异反映在增殖差异上。一个表达人IL-2rα和IL-2rβ以及鼠γc的细胞系仅在低剂量人IL-2刺激下才会强烈增殖，而人和鼠IL-2均可刺激含有鼠IL-2rα（以及人IL-2rβ和鼠γc）的细胞系增殖。因此，IL-2rα是主要负责配体结合物种特异性的链。
