cDNAs encoding the human receptor for interleukin-2 (IL-2, T-cell growth factor) have been molecularly cloned and the receptor protein biochemically characterized. The human genome contains a single receptor gene located on chromosome 10P band 14-15 and organized within eight separate exons. Transcription of this receptor gene results in three differently sized classes of mRNA varying in length due to the use of at least three different polyadenylation signals. Alternate splicing may also occur which results in removal of a 216 base pair segment corresponding to exon 4. This aberrantly spliced mRNA does not appear to encode a protein capable of binding IL-2 or anti-Tac. The mature IL-2 receptor protein is composed of 251 amino acids. This peptide (Mr 33,000) is cotranslationally modified by addition of N-linked carbohydrate producing two precursor forms (Mr 35,000 and 37,000). These precursors are subsequently exported to the Golgi apparatus where 0-linked sugar, sialic acid, and sulfate are added prior to display of the mature receptors (Mr 55,000) on the cell surface. T-cell activation is characterized by an early rise and later fall in IL-2 receptor expression which is involved in the regulation of the T-cell immune response. The variable expression of IL-2 receptors is controlled, at least in part, at the level of receptor gene transcription. IL-2 receptors can be reinduced in """"""""senescent"""""""" activated T-cells, which have lost greater than 90% of their receptors, by stimulation with antigen or mitogen, agents which activate protein kinase C (PMA, phospholipase C, diacylglycerol congeners) and IL-2. Human T-cell leukemia-lymphoma virus I (HTLV-I)-infected adult T-cell leukemia (ATL) cells uniformly express large numbers of IL-2 receptors. The amplified expression of receptors in ATL cells involves constitutive transcription of the IL-2 receptor gene and use of three rather than two promoters. Agents which activate normal IL-2 receptor gene transcription may selectively inhibit receptor transcription in ATL cells. ATL cells can be selectively killed with anti-IL-2 receptor antibodies coupled to the toxic A chain of ricin.
