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 the magnitude and duration of T cell expansion required in an immune response. 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 components of high-affinity receptors (alpha beta gamma) are continuously internalized in the absence as well as in the presence of IL-2. From studies on other receptors, it is known that endocytosis of ligand-receptor complexes is due to an intrinsic property of the receptor. However, the specific chains responsible for endocytosis of high-affinity IL-2 receptors have not been fully elucidated. IL-2R gamma has been reported 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 receptors to allow for its internalization. From the reported results on IL-2 internalization in transfected fibroblasts, it cannot be concluded as to the respective roles of IL-2R beta and/or IL-2R gamma in endocytosis. As modulation of receptor number is important for biological activity, we have attempted to define the chains responsible for receptor internalization. In this work, we have studied the endocytic properties of IL-2R beta. We demonstrate that IL-2R beta is constitutively endocytosed in a B cell line, derived from a X-linked severe combined immunodeficiency patient, which lacks expression of IL-2R gamma. IL-2R beta was also constitutively internalized in T and natural killer cell lines independently of IL-2R gamma. These results suggest that IL-2R beta is endowed with endocytic capacity and carries internalization signals.
Hémar
A
A
Unité de Biologie des Interactions Cellulaires, CNRS URA 361, Institut Pasteur, Paris, France.
Lieb
M
M
Subtil
A
A
DiSanto
J P
JP
Dautry-Varsat
A
A
D000911:Antibodies, Monoclonal; D002461:Cell Line, Transformed; D004705:Endocytosis / Q000502:physiology*; D006207:Half-Life; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D008214:Lymphocytes / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D016511:Severe Combined Immunodeficiency / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D015375:Receptors, Interleukin-2