title: Interleukin 2 receptor-targeted cytotoxicity. Interleukin 2 receptor-mediated action of a diphtheria toxin-related interleukin 2 fusion protein.
abstract: The IL-2 toxin-mediated inhibition of protein synthesis in high affinity IL-2-R-positive murine and human T cell lines has been examined. Both excess free IL-2 and mAb to the Tac epitope of the p55 subunit of IL-2-R are shown to block the action of IL-2 toxin; whereas, agents that interact with other receptors or antigens on the T cell surface have no effect. We show that IL-2 toxin, like diphtheria toxin, must pass through an acidic vesicle in order to intoxicate target T cells. Finally, we demonstrate that the IL-2 toxin-mediated inhibition of protein synthesis in both human and murine T cells that bear the high affinity IL-2-R is due to the classic diphtheria toxin fragment A-catalyzed ADP ribosylation of elongation factor 2.
mesh_terms: D036002:ADP Ribose Transferases; D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004167:Diphtheria Toxin / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D010430:Pentosyltransferases / Q000378:metabolism; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000187:drug effects* / Q000502:physiology; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology*
chemical_list: D004167:Diphtheria Toxin; D000922:Immunotoxins; D007376:Interleukin-2; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors; D011500:Protein Synthesis Inhibitors; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D036002:ADP Ribose Transferases; D010430:Pentosyltransferases