Internalization of interleukin 2 (IL-2) by high affinity IL-2 receptors is required for the growth of IL-2-dependent T cell lines.
During the growth of interleukin 2 (IL-2)-dependent T cells IL-2 binding is followed by internalization of the complex between IL-2 and the high affinity IL-2 receptor (HA-IL-2R). The respective role of IL-2 binding to HA-IL-2R and internalization of the complex has been examined. Monoclonal antibody 7D4 (IgM) blocks IL-2-dependent T cell growth although it does not affect IL-2 binding to HA-IL-2R. We show here that 7D4 inhibits T cell growth by blocking IL-2 internalization by HA-IL-2R. In contrast, Fab fragments prepared from 7D4 neither block IL-2 internalization nor inhibit T cell growth. Monoclonal 5A2, that recognizes an epitope related to the IL-2 binding site as well as its Fab fragment, inhibits T cell growth and IL-2 internalization. Monoclonal antibody 7D4, because of its pentameric structure, probably aggregates the IL-2R at the T cell surface and therefore prevents it internalization. The data presented in this paper suggest that simple occupancy of HA-IL-2R by IL-2 is not sufficient to transduce the T cell growth signal; this signal is transmitted only after internalization of the IL-2/HA-IL-2R complex.
D000911:Antibodies, Monoclonal / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004705:Endocytosis; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007376:Interleukin-2 / Q000378:metabolism* / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2