Ferrer M, Hémar A, Duprez V, Hellio R, Dautry-Varsat A
Unité de Biologie des Interactions Cellulaires, CNRS URA 361, Institut Pasteur, Paris/France.
Eur J Cell Biol. 1993 Apr;60(2):276-82.
The growth factor interleukin 2 (IL2) binds to high and low-affinity receptors (Kd approximately 10-100 pM and 10 nM, respectively) present on activated T lymphocytes. High-affinity receptors are composed of two non-convalently linked polypeptides, alpha and beta of 55 and 70 kDa. These two polypeptides do not share any sequence homology, but each of them, in the absence of the other, binds IL2: alpha with a Kd approximately 10 nM and beta with a Kd approximately 1 nM. When these two chains are associated in lymphocytes, they form high-affinity receptors that mediate IL2 endocytosis and degradation, and transduce IL2 signaling. On cells that physiologically express IL2 receptors, such as activated T lymphocytes, both high and low affinity-receptors are present simultaneously on the cell surface, and low-affinity receptors (alpha without beta) are, in most instances, more abundant by a factor 5 to 10 than high-affinity receptors (alpha associated to beta). Low-affinity receptors bind IL2 but do not induce its internalization and signaling. The physiological role of the complexity of this receptor system is not fully understood. In the present study, we have investigated directly the fate of the high-affinity receptors when the ligand is endocytosed. By confocal microscopy, using two monoclonal antibodies specific for alpha and for beta, respectively, we show that each of these two polypeptides is located in intracellular endocytic compartments. Therefore, when the alpha chain is part of high-affinity receptors, it is endocytosed, as opposed to when it is part of low-affinity receptors and is not endocytosed.(ABSTRACT TRUNCATED AT 250 WORDS)
生长因子白细胞介素2（IL2）与活化T淋巴细胞上存在的高亲和力和低亲和力受体（解离常数分别约为10 - 100 pM和10 nM）结合。高亲和力受体由两条非共价连接的多肽组成，分别为55 kDa和70 kDa的α链和β链。这两条多肽没有任何序列同源性，但它们各自在没有对方的情况下都能结合IL2：α链的解离常数约为10 nM，β链的解离常数约为1 nM。当这两条链在淋巴细胞中结合时，它们形成介导IL2内吞作用和降解并转导IL2信号的高亲和力受体。在生理上表达IL2受体的细胞，如活化的T淋巴细胞上，高亲和力和低亲和力受体同时存在于细胞表面，并且在大多数情况下，低亲和力受体（α链无β链）比高亲和力受体（α链与β链结合）丰富5到10倍。低亲和力受体结合IL2但不诱导其内化和信号传导。这种受体系统复杂性的生理作用尚未完全了解。在本研究中，我们直接研究了配体内吞时高亲和力受体的命运。通过共聚焦显微镜，分别使用针对α链和β链的两种单克隆抗体，我们表明这两条多肽中的每一条都位于细胞内吞小室中。因此，当α链是高亲和力受体的一部分时，它会被内吞，这与它作为低亲和力受体的一部分时不被内吞相反。（摘要截断于250字）
