title: Lack of intermediate-affinity interleukin-2 receptor in mice leads to dependence on interleukin-2 receptor alpha, beta and gamma chain expression for T cell growth.
abstract: An interleukin (IL)-4 dependent mouse T cell clone 8.2 derived from an IL-2-dependent T cell line was characterized. As measured by flow cytometric analysis and Northern blotting, it expresses IL-2 receptor beta (IL-2R beta) and gamma (IL-2R gamma) chains, but has lost expression of IL-2 receptor alpha chain (IL-2R alpha). To investigate the properties of the mouse IL-2R beta gamma complex and the role of IL-2R alpha gene expression, this clone was further studied. T cell clone 8.2 has lost the capacity to bind 125I-labeled human IL-2 under experimental conditions able to detect intermediate-affinity IL-2R in human cells. Mouse IL-2 is unable to block the binding of mAb TM beta 1 to 8.2 cells. Under the same experimental conditions, mouse IL-2 blocks the binding of TM beta 1 to C30-1 cells expressing the IL-2 alpha beta gamma complex. Since TM beta 1 recognizes an epitope related to the IL-2 binding site of IL-2R beta, these results can be taken as a demonstration that mouse IL-2R beta gamma does not bind mouse IL-2. Furthermore, T cell clone 8.2 does not proliferate in response to recombinant mouse or human IL-2. On the other hand, T cell transfectant lines expressing heterospecific receptors made of the human IL-2R beta and mouse IL-2R gamma chains bind 125I-labeled human IL-2 and proliferate in response to IL-2. This establishes the difference between mouse and human IL-2R beta chains. Transfection of T cell clone 8.2 with human IL-2R alpha genes restores their capacity to proliferate in response to IL-2. In addition, all transfectants grown in IL-2 express the endogeneous mouse IL-2R alpha chain. When grown in IL-4, the endogeneous mouse IL-2R alpha gene remains silent in all these transfectants. These results show that, contrary to the human, the mouse does not express an intermediate-affinity IL-2R. Expression of the IL-2R alpha gene is therefore required for the formation of the functional IL-2R in mice.
authors.affiliation: Unité d'Immunogénétique Cellulaire, Institut Pasteur, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Chastagner
authors.forename: J L
authors.initials: JL
authors.lastname: Moreau
authors.forename: Y
authors.initials: Y
authors.lastname: Jacques
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Miyasaka
authors.forename: M
authors.initials: M
authors.lastname: Kondo
authors.forename: K
authors.initials: K
authors.lastname: Sugamura
authors.forename: J
authors.initials: J
authors.lastname: Thèze
mesh_terms: D000818:Animals; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry; D008213:Lymphocyte Activation; D051379:Mice; D011485:Protein Binding / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2