The interleukin-2 receptor on malignant cells: a target for diagnosis and therapy.
Interleukin-2 (IL-2) is a lymphokine synthesized by T cells following activation. Resting T cells do not express IL-2 receptors, but receptors are rapidly expressed on T cells following interaction of the antigen-specific T-cell-receptor complex with appropriately processed and presented antigens. Anti-Tac, a monoclonal antibody that recognizes the IL-2 receptor, has been used to purify the receptor. The receptor is a 55-kDa glycoprotein comprised of 251 amino acids including a single 19-amino 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-cell lymphotrophic virus (HTLV-I)-associated adult T-cell leukemia (ATL) expressed the Tac antigen. In HTLV-I-infected cells, the 42-kDa long open reading frame (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 the ATL cells may play a role in the uncontrolled growth of these leukemic T cells. Patients with the Tac-positive ATL are being treated with both unmodified and toxin-conjugated forms of anti-Tac monoclonal antibody directed toward this growth factor receptor.
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology; D004247:DNA / Q000032:analysis; D017977:Deltaretrovirus; D006801:Humans; D007938:Leukemia / Q000175:diagnosis* / Q000628:therapy; D011971:Receptors, Immunologic / Q000032:analysis* / Q000276:immunology; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000032:analysis*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D004247:DNA