Studies on the interleukin-2 receptor, its generation and dynamics using monoclonal anti-interleukin-2 receptor antibodies.
There is increasing evidence suggesting that the monoclonal antibodies ART-18, AMT-13 and anti-Tac recognize species-specific antigenic determinants of the interleukin-2 (IL-2) receptors of rat, mouse and human origin, respectively. In order to compare directly the molecules (glycoproteins) recognized by these antibodies, concanavalin A (ConA) activated T-lymphocytes of the respective species were surface labeled with 125I, after which the materials immunoprecipitated by the appropriate anti-IL-2 receptor antibodies were subjected to SDS-PAGE analysis. The noncross-reacting antibodies ART-18 and AMT-13 both precipitated a 50-55-kD molecule. The anti-Tac-reactive material (the putative human IL-2 receptor) is considerably different (60-65 kD) from those precipitated by antibodies ART-18 and AMT-13 (the putative rat and mouse IL-2 receptors). An indirect binding assay using the anti-mouse IL-2 receptor antibody AMT-13 showed that, after addition of ConA to spleen cell cultures, T-lymphocytes expressed IL-2 receptors before the onset of the ConA-induced DNA synthesis. The ConA-induced expression of the IL-2 receptor is apparently a transient event. IL-2 receptor bearing cells progressively lost their receptors (within 6 days) when recultured in the absence of ConA. Cells re-exposed to ConA regained IL-2 receptors. Short exposure of T-cells (thymocytes) to ConA or the nonmitogenic compound phorbol myristate acetate (PMA) is not sufficient to trigger IL-2 receptor expression. Murine thymocytes incubated with PMA for 30 min or with ConA for 4 hr (mitogen-pulsed T-cells) failed to bind the anti-IL-2 receptor antibody AMT-13 and to absorb IL-2 activity present in semipurified IL-2 preparations, but they proliferated vigorously in response to the same IL-2 preparations. The IL-2 preparations, when absorbed with thymocytes, lost: (1) the capacity to generate IL-2 receptors, and (2) the capacity to induce proliferation of mitogen-pulsed cells; but they retained the capacity to induce proliferation of T-lymphoblasts. These results suggest the existence of a factor, IL-2 receptor inducing factor (RIF), present in the IL-2 preparations. It is postulated that RIF is a prerequisite for the acquisition of IL-2 receptors and consequently for IL-2 responsiveness by lectin-activated cells.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000954:Antigens, Surface / Q000032:analysis; D002455:Cell Division; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011917:Rats, Inbred Lew; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000276:immunology; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; D013755:Tetradecanoylphorbol Acetate