Interleukin 2 (IL-2) receptor expression and sensitivity to diphtheria fusion toxin DAB₃₈₉IL-2 in cultured hematopoietic cells

The high-affinity interleukin 2 (IL-2) receptor is a heterotrimer consisting of α, β, and γ subunits. We examined the concentration of subunit mRNA for each of the three protein subunits on human hematopoietic cell lines, human peripheral blood mononuclear cells, and murine fibroblasts transfected with cDNAs encoding the human IL-2 receptor subunits. In most cultured hematopoietic cells, there was abundant γ subunit message. In contrast, there was variable expression of both α and β subunit message. Sensitivity of cells to the diphtheria fusion toxin DAB₃₈₉IL-2 was not related to expression of any single IL-2 receptor subunit mRNA. Rather, the greatest sensitivity was observed for cells possessing all three subunit mRNAs. Cells displaying β and γ subunit mRNA showed a reduced but significant sensitivity to the fusion toxin. In contrast, cells with α and γ subunit mRNA, but missing the β subunit mRNA, were insensitive to DAB₃₈₉IL-2. The data correlate with the requirement for an intermediate or a high-affinity receptor for cell intoxication. A critical concentration of the β subunit may be required for toxin internalization and killing.