BOTH THE ALPHA-CHAINS 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 r eceptors (Kd almost-equal-to 10-100 pm and 10 nm, respectively) presen t on activated T lymphocytes. High-affinity receptors are composed of two non-convalently linked polypeptides, alpha and beta of 55 and 70 k Da. These two polypeptides do not share any sequence homology, but eac h of them, in the absence of the other, binds IL2: alpha with a Kd alm ost-equal-to 10 nM and beta with a Kd almost-equal-to 1 nm. When these two chains are associated in lymphocytes, they form high-affinity rec eptors 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 p resent 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 s ystem is not fully understood. In the present study, we have investiga ted directly the fate of the high-affinity receptors when the ligand i s endocytosed. By confocal microscopy, using two monoclonal antibodies specific for alpha and for beta, respectively, we show that each of t hese two polypeptides is located in intracellular endocytic compartmen ts. Therefore, when the alpha chain is part of high-affinity receptors , it is endocytosed, as opposed to when it is part of low-affinity rec eptors and is not endocytosed. In previous studies, the half-life of a lpha on the cell surface has been measured and found to be long (about 48 h), while the half-life of high-affinity receptors is very short ( about 15-30 min). Taking this into account, our results suggest that, after endocytosis of high-affinity receptors complexes, its two compon ents alpha and beta have a different fate: beta being degraded while a lpha would recycle back to the cell surface. This model predicts that the two chains of high-affinity receptors are sorted towards different intracellular routes, i.e., recycling to the plasma membrane or degra dation. If such a mechanism exists, it remains to be unraveled.