Both the alpha and beta chains of high-affinity interleukin 2 receptors are located in intracellular vesicles when their ligand is endocytosed.
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)
Ferrer
M
M
Unité de Biologie des Interactions Cellulaires, CNRS URA 361, Institut Pasteur, Paris/France.
Hémar
A
A
Duprez
V
V
Hellio
R
R
Dautry-Varsat
A
A
D020126:Brefeldin A; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D008970:Molecular Weight; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D003517:Cyclopentanes; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D020126:Brefeldin A; D003513:Cycloheximide