Resting T cells do not express high-affinity IL-2 receptors, but receptors are rapidly expressed on T cells after activation with antigen or mitogen. We, have identified two peptides that bind IL-2, the 55 kD peptide reactive with the anti-Tac monoclonal and a novel 70/75 kD (p75) peptide. We have proposed a multichain model for the high-affinity IL-2 receptor in which both the p55 Tac and the p75 IL-2 binding peptide are associated in the receptor complex. Using crosslinking, coprecipitation, and fluorescence energy transfer techniques, additional p22, p35, p4O, p95, and pl8O peptides have been identified that may be associated with the 55 kD Tac peptide in the multichain receptor. T cells in patients with certain lymphoid malignancies, select autoimmune disorders as well as individuals rejecting allografts express the IL-2 receptors identified by the anti-Tac monoclonal antibody whereas normal resting cells do not. To exploit this differential expression, a wide variety of IL-2 receptor-directed therapeutic reagents have been generated including unmodified anti-Tac, toxin conjugates of anti-Tac, radioisotopic chelates of anti-Tac as well as hyperchimeric """"""""humanized"""""""" anti-Tac antibodies that are entirely human except for the small hypervariable segments from the mouse antibody. The clinical application of these highly potent IL-2-receptor directed agents represents a new therapeutic perspective for certain neoplastic diseases, autoimmune disorders, and for the prevention of allograft rejection.
