Nakamura Y, Russell S M, Mess S A, Friedmann M, Erdos M, Francois C, Jacques Y, Adelstein S, Leonard W J
Section on Pulmonary and Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Nature. 1994 May 26;369(6478):330-3. doi: 10.1038/369330a0.
The interaction of interleukin-2 (IL-2) and IL-2 receptors critically regulates the T-cell immune response following antigen activation. IL-2 can signal through high or intermediate affinity receptors which contain IL-2R alpha (refs 3, 4) +beta (refs 5-8) +gamma (ref. 9) or beta+gamma chains, respectively. IL-2R gamma is a common gamma chain, gamma c, also shared by the IL-7 (ref. 10) and IL-4 (refs 11, 12) receptors, which when mutated results in X-linked severe combined immunodeficiency. Using chimaeric receptor constructs together with monoclonal or bispecific antibodies we demonstrate here that IL-2 signalling requires ligand-induced extracellular-domain-mediated heterodimerization of the beta- and gamma c-chain cytoplasmic domains. Anti-IL-2R alpha monoclonal antibodies trigger proliferation of cells transfected with chimaeric constructs in which the extracellular domains of IL-2R beta and gamma c are replaced by that of IL-2R alpha. Other experiments using chimaeric constructs indicated that IL-2 binds monomerically and monovalently to IL-2R alpha and that the beta-transmembrane domain is not required for receptor chain interactions. Finally, we provide a method for mapping residues in the gamma c cytoplasmic domain even in cells that constitutively express gamma c.
白细胞介素-2（IL-2）与IL-2受体的相互作用在抗原激活后对T细胞免疫反应起着关键的调节作用。IL-2可通过高亲和力或中等亲和力受体发出信号，这些受体分别包含IL-2Rα（参考文献3、4）+β（参考文献5 - 8）+γ（参考文献9）或β + γ链。IL-2Rγ是一种共同的γ链，γc，也为IL-7（参考文献10）和IL-4（参考文献11、12）受体所共有，当其发生突变时会导致X连锁严重联合免疫缺陷。在此，我们使用嵌合受体构建体以及单克隆或双特异性抗体证明，IL-2信号传导需要配体诱导的β链和γc链胞质结构域的细胞外结构域介导的异源二聚化。抗IL-2Rα单克隆抗体可触发用嵌合构建体转染的细胞增殖，在这些构建体中，IL-2Rβ和γc的细胞外结构域被IL-2Rα的细胞外结构域所取代。使用嵌合构建体的其他实验表明，IL-2以单体和单价形式与IL-2Rα结合，并且受体链相互作用不需要β跨膜结构域。最后，我们提供了一种即使在组成性表达γc的细胞中也能定位γc胞质结构域中残基的方法。
