The multichain interleukin-2 receptor: a target for immunotherapy of patients receiving allografts.
Antigen-induced activation of resting T cells induces the synthesis of interleukin-2 (IL-2) as well as the expression of specific cell surface high-affinity receptors for this lymphokine. There are at least two forms of the cellular receptors for IL-2, one with a very high affinity and the other with a lower affinity. Two IL-2 binding peptides, a 55-kd peptide reactive with the anti-Tac monoclonal antibody and a 75-kd, non-Tac IL-2-binding peptide, were identified. A multichain model for the high-affinity receptor in which an independently existing p55 or p75 peptide would represent low-or intermediate-affinity receptors, respectively, and high-affinity receptors would be expressed when both of these receptors are expressed and associated in a receptor complex, is proposed. An additional 95 - to 105-kd peptide may also participate in the multisubunit, high-affinity form of the IL-2 receptor. The p75 peptide is receptor for IL-2 on large granular lymphocytes and is sufficient for the IL-2 activation of these cells. In contrast to resting T cells, the T cells of patients with certain neoplasias of mononuclear cells and of patients with select autoimmune disorders, as well as T cells participating in organ allograft rejections, express the Tac antigen. To exploit the fact that IL-2 receptors are present on abnormally activated T cells but no on normal resting T cells, clinical trials have been initiated involving patients with neoplastic or autoimmune disorders as well as those receiving organ allografts. These patients are being treated with unmodified anti-Tac, with isotopic (212 Bi and 90Y) chelates of anti-Tac, with truncated Pseudomonas toxin conjugates of anti-Tac or IL-2, and with recombinant chimeric "humanized" anti-Tac.
Waldmann
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Metabolism Branch National Cancer Institute, Bethesda, MD 20892.
Goldman
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D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000628:therapy; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000276:immunology*; D015458:Leukemia, T-Cell / Q000628:therapy; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000648:ultrastructure; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D015375:Receptors, Interleukin-2