ROLE AND MOLECULAR BIOLOGY OF THE INTERLEUKIN-2-INTERLEUKIN-2 RECEPTOR SYSTEM IN HEALTH AND DISEASE

Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.

ROLE AND MOLECULAR BIOLOGY OF THE INTERLEUKIN-2-INTERLEUKIN-2 RECEPTOR SYSTEM IN HEALTH AND DISEASE

Progress in Immunology VI. Sixth International Congress of Immunology. Cinader B, Miller RG, eds. New York, Academic Press, p. 553-62, 1986.. Unique Identifier : AIDSLINE ICDB/88640034
Waldmann TA; Kozak RW; Tsudo M; Oh-ishi T; Bongiovanni KF; Goldman CK; Metabolism Branch, NCI, Bethesda, MD 20892

Abstract: Anti-Tac, a monoclonal antibody that recognizes the interleukin-2 (IL-2) receptor, was used to (1) characterize the human IL-2 receptor; (2) molecularly clone cDNA for the human IL-2 receptor peptide; (3) define lymphocyte functions that require interaction of IL-2 with its receptor; (4) analyze disorders of IL-2 receptor expression on leukemic cells; and (5) develop protocols for the therapy of patients with IL-2 receptor-expressing adult T cell leukemia (ATL) and autoimmune disorders and for individuals receiving organ allografts. The receptor is a 55-kD glycoprotein of 251 amino acids, a single 19-amino acid transmembrane domain, and a short intracytoplasmic domain composed of 13 amino acids at the carboxy-terminus. Normal resting T cells and most leukemic T cell populations examined did not express IL-2 receptors; however, the leukemic cells of all patients with human T lymphotropic virus (HTLV)-I-associated ATL expressed the Tac antigen. In HTLV-I-infected cells, the 42-kD tat protein, encoded in part by the tat region of HTLV-I, may act as a transacting activator that induces transcription of the IL-2 receptor gene, thus providing an explanation for the constant association of HTLV-I infection of lymphoid cells and IL-2 receptor expression. The constant display of large numbers of IL-2 receptors, which may be aberrant in ATL cells, may play a role in the uncontrolled growth of these leukemic cells. Therapeutic studies performed clinically and in vitro have involved the use of IL-2 receptor as a target and the anti-Tac monoclonal antibody, alone or conjugated with the toxin ricin or with 212Bi, an alpha-emitting radionuclide. (47 Refs)

Keywords: Antigens, Surface/GENETICS Autoimmune Diseases/GENETICS *Cloning, Molecular DNA/GENETICS Gene Expression Regulation Human HTLV-BLV Infections/IMMUNOLOGY Immunologic Deficiency Syndromes/*GENETICS Interleukin-2/*GENETICS Peptides/GENETICS Receptors, Immunologic/*GENETICS RNA, Messenger/GENETICS T-Lymphocytes/*IMMUNOLOGY Transplantation Immunology MEETING PAPER

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