Binding, uptake and degradation of human recombinant interleukin-2 (125 ala) in activated human T- and B-lymphocytes and in monocyte-macrophages.
High-affinity receptors for IL-2 (ala 125) were demonstrated in PHA-, antigen- and/or alloantigen-activated human T-cells (both proliferative and cytotoxic), in PWM-activated human B-cells and in human monocyte-macrophages. Binding in PHA-blasts was irreversible and Ca++-independent, and labelled IL-2 (ala 125) bound at 4 degrees C could not be removed by trypsin treatment. Binding was strongly pH-dependent, and lowering of pH caused release of nearly all cell associated radioactivity at 4 degrees C. In T- and B-lymphocytes, additional binding at high ligand concentrations was accounted for by receptors of much lower affinity. Binding to low-affinity receptors appeared reversible. At 4 degrees C, 2.2 pM labelled IL-2 (ala 125) bound to PHA-blasts (3.6 X 10(6)/ml) with a half time of about 15 min, and the association rate constant was approximately 8 X 10(9) M-1 min-1. The number of high affinity receptors per T-cell was determined as 9.7 +/- 0.5 X 10(2). At 37 degrees C, 60% of the tracer bound at 4 degrees C was rapidly internalized (Kint = 0.89 X 10(-1) min-1), and radioactivity comprising small MW products and iodotyrosine was released following a sigmoidal curve after a 20 min lag period. Similar results were obtained in PWM-activated B-lymphocytes and in cultured monocytes. It is concluded that high-affinity receptors mediate binding, uptake and degradation of IL-2 in activated human T- and B-lymphocytes and in monocyte-macrophages.
D001402:B-Lymphocytes / Q000276:immunology; D001693:Biological Transport, Active; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology
D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2