Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
STRUCTURE AND FUNCTION OF THE HUMAN INTERLEUKIN-2 RECEPTOR
Oncogenes and Growth Control. Kahn P et al, eds. New York, Springer-Verlag, p. 128-34, 1986.. Unique Identifier : AIDSLINE ICDB/87637978 Hatakeyama M; Minamoto S; Mori H; Taniguchi T; Inst. for Molecular and Cell Biology, Osaka Univ., 1-3,; Yamadaoka, Suita-shi, Osaka 565, Japan
Abstract:
The main features of the human interleukin-2 receptor (IL2R) and the relationship of IL2R to T cell growth control are reviewed under the following headings: IL2-receptor binding; analysis of the IL2R/Tac antigen; phosphorylation of IL2R; IL2 as a growth inhibitor; IL2 and oncogene expression; and IL2R and adult T cell leukemia. The magnitude of the growth response of IL2-dependent T cells to IL2 is determined both by the IL2 concentration and by the number of functional, high-affinity surface IL2Rs on the responder cells. A monoclonal antibody has been prepared that specifically reacts with activated, but not resting, human T cells and that blocks IL2-dependent T cell growth; it also blocks the binding of IL2 to IL2R-bearing T cells. The antigen recognized by this antibody, designated the Tac antigen, may be the human IL2R or molecules closely associated with it. The Tac antigen is encoded by a single gene on human chromosome 10; the gene is divided into 8 exons and 7 introns and spans more than 25 kb. The Tac antigen contains only a 13-amino acid cytoplasmic domain. Transfection of an expression vector (in which the Rous sarcoma virus long terminal repeat sequence was linked upstream of the Tac antigen cDNA) into the mouse thymoma (T lymphoid) cell line EL-4 (which has the Thy1+, Ly1+, Lyt2-, and L3T4+ phenotype, but does not express IL2R) resulted in the expression of high- as well as low-affinity IL2Rs. These results demonstrated that the two classes of human IL2R can be generated from a single gene and that the Tac antigen itself is a constituent of both high- and low-affinity IL2Rs in lymphocytes. Recent studies have shown that treatment of T cells expressing IL2R with IL2 stimulates expression of the c-myc and c-myb oncogenes. Preliminary analysis of the levels of several c-onc mRNAs in mouse EL-4 transformants before and after treatment with IL2 suggests that the level of c-myc mRNA decreases following IL2 treatment, whereas that of other oncogenes, including the ras gene family, are unaffected. Adult T cell leukemia (ATL) cells generally do not produce IL2 or respond to exogenous IL2; this finding argues against the hypothesis that an IL2/IL2R autocrine mechanism operates in ATL leukemogenesis. Mechanisms that might account for this aberrant expression of IL2R in ATL cells are discussed. (29 Refs)
Keywords: Amino Acid Sequence Animal Antigens, Surface/PHYSIOLOGY Cell Division Cell Line Cell Transformation, Neoplastic Gene Expression Regulation Human HTLV-BLV Infections/GENETICS Interleukin-2/*PHYSIOLOGY Oncogenes Phosphorylation Receptors, Immunologic/GENETICS/*PHYSIOLOGY T-Lymphocytes/IMMUNOLOGY MONOGRAPH
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Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
