Interleukin 2 receptor-targeted cytotoxicity. Interleukin 2 receptor- mediated action of a diphtheria toxin-related interleukin 2 fusion protein

doi:10.1084/jem.167.2.612

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Interleukin 2 receptor-targeted cytotoxicity. Interleukin 2 receptor- mediated action of a diphtheria toxin-related interleukin 2 fusion protein

P Bacha, DP Williams, C Waters, JM Williams, JR Murphy and TB Strom
Seragen, Inc., Hopkinton, Massachusetts 01748.

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.
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