ENDOCYTOSIS OF THE BETA-CHAIN OF INTERLEUKIN-2 RECEPTOR REQUIRES NEITHER INTERLEUKIN-2 NOR THE GAMMA-CHAIN

Interleukin-2 (IL-2) and IL-2 receptors (IL-2R) critically regulate th e magnitude and duration of T cell expansion required in an immune res ponse. Modulation occurs at the level of receptor number and affinity. IL-2R is a multisubunit receptor which contains at least three chains , IL-2R alpha (p55), IL-2R beta (p70) and IL-2R gamma (p64). Some comp onents of high-affinity receptors (alpha beta gamma) are continuously internalized in the absence as well as in the presence of IL-2. From s tudies on other receptors, it is known that endocytosis of ligand-rece ptor complexes is due to an intrinsic property of the receptor. Howeve r, the specific chains responsible for endocytosis of high-affinity IL -2 receptors have not been fully elucidated. IL-2R gamma has been repo rted to be necessary for IL-2 internalization, based on the fact that fibroblasts transfected with IL-2R alpha and -beta do not internalize IL-2. However, IL-2 dissociates too rapidly from IL-2R alpha beta rece ptors to allow for its internalization. From the reported results on I L-2 internalization in transfected fibroblasts, it cannot be concluded as to the respective roles of IL-2R beta and/or IL-2R gamma in endocy tosis. As modulation of receptor number is important for biological ac tivity, we have attempted to define the chains responsible for recepto r internalization. In this work, we have studied the endocytic propert ies of IL-2R beta. We demonstrate that IL-2R beta is constitutively en docytosed in a B cell line, derived from a X-linked severe combined im munodeficiency patient, which lacks expression of IL-2R gamma. IL-2R b eta was also constitutively internalized in T and natural killer cell lines independently of IL-2R gamma. These results suggest that IL-2R b eta is endowed with endocytic capacity and carries internalization sig nals.