Abstract:
Interleukin-2 (IL-2) is a lymphokine synthesized by some T cells following activation. Resting T cells do not express IL-2 receptors but receptors are rapidly expressed on T cells following the interaction of antigens, mitogens, or monoclonal antibodies with the antigen specific T-cell receptor complex. Using anti-Tac a monoclonal antibody that recognizes the IL-2 receptor, the receptor has been purified. The receptor is a 33 kdalton peptide that is post-translationally glycosylated to a 55 kdalton mature form. Mature receptors contain both N-linked and O-linked sugars and are both sulfated and phosphorylated. Using an oligonucleotide probe, based on the N-terminal amino acid sequence, cDNAs encoding this receptor have been cloned, sequenced and expressed. The addition of anti-Tac to in vitro culture systems blocks the IL-2 induced DNA synthesis of IL-2 dependent T-cell lines and inhibits soluble auto- and alloantigen induced T-cell proliferation. Furthermore, it prevents the generation of cytotoxic and suppressor effector T cells. The anti-receptor antibody also inhibits lectin stimulated immunoglobulin synthesis and the sequential expression of late appearing activation antigens on T cells. Normal resting T cells and most leukemic T-cell populations do not express IL-2 receptors however the leukemic cells of all patients with human T-cell leukemia/lymphoma virus (HTLV-I) associated, adult T-cell leukemia (ATL) examined expressed the Tac antigen. In HTLV-I infected cells the 42 kdalton long open reading frame (LOR) protein encoded in part, by the pX region of HTLV-I may act as a transacting transcriptional 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 an anti-Tac monoclonal antibody directed towards this growth factor receptor.
Keywords: Antibodies, Monoclonal/THERAPEUTIC USE Antigens, Surface/IMMUNOLOGY Cloning, Molecular DNA/ANALYSIS Human HTLV-BLV Viruses Leukemia/*METABOLISM/THERAPY Lymphocyte Transformation Receptors, Immunologic/*ANALYSIS/GENETICS Retroviridae Infections/*METABOLISM/THERAPY T-Lymphocytes JOURNAL ARTICLE
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